Brintellix weight gain reviews

Side effects. Hmmm.

Suicidal Thoughts and Actions and Antidepressant DrugsAntidepressants may increase suicidal thoughts or actions in some children, teens or young adults within the first few months of treatment or when the dose is changed. Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. People who have (or have a family history of) bipolar illness, or suicidal thoughts or actions may have a particularly high risk. Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts or feelings. Call your healthcare provider right away if symptoms such as anxiety, irritability, impulsivity, trouble sleeping, aggressive behavior or suicidal thoughts are new, worse or worry you. TRINTELLIX has not been evaluated for use in patients under 18.Do not take TRINTELLIX if you:Are allergic to vortioxetine or any of the ingredients in TRINTELLIXTake a Monoamine Oxidase Inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid; do not take an MAOI within 21 days of stopping TRINTELLIX; do not start TRINTELLIX if you stopped taking an MAOI in the last 14 daysTRINTELLIX may cause serious side effects including:Serotonin Syndrome: A potentially life-threatening problem that can happen when medicines such as TRINTELLIX are taken with certain other medicines. Symptoms may include agitation, hallucinations, coma or other changes in mental status; problems controlling movements or muscle twitching, stiffness or tightness; fast heartbeat, high or low blood pressure; sweating or fever; nausea, vomiting or diarrhea.Abnormal bleeding or bruising: TRINTELLIX and other serotonergic antidepressant medicines may increase your risk of bleeding or bruising, especially if you take the blood thinner warfarin (Coumadin®, Jantoven®), a non-steroidal anti-inflammatory drug (NSAID), or aspirin.Manic episode: Symptoms may include greatly increased energy; severe trouble sleeping; racing thoughts; reckless behavior; unusually grand ideas; excessive happiness or irritability; talking more or faster than usual.Visual problems: May include eye pain, changes in vision, swelling or redness in or around the eye. Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are.Low salt (sodium) levels in the blood: Symptoms may include headache; difficulty concentrating, memory changes or confusion; weakness and unsteadiness on your feet; and in severe or sudden cases hallucinations, fainting, seizures or coma. If not treated, severe low sodium levels can cause death.Before starting TRINTELLIX, tell your healthcare provider if you have or had liver problems, seizures or convulsions, bipolar disorder (manic depression) or mania, low salt (sodium) levels in your blood, bleeding problems, drink alcohol, have any other medical conditions or if you are pregnant, nursing, plan to become pregnant, or plan to nurse.TRINTELLIX and some medicines may interact with each other, may not work as well, or may cause serious side effects when taken together. Tell your healthcare provider if you plan on or are taking any other prescription and non-prescription medicines, vitamins and herbal supplements including medicines for migraine headaches, such as triptans; medicines used to treat mood, anxiety, psychotic or thought disorders such as tricyclics, lithium, SSRIs, SNRIs, bupropion, buspirone or antipsychotics; MAOIs including linezolid (a specific antibiotic); over-the-counter supplements such as tryptophan or St. John’s wort; and the following medicines: aspirin, NSAIDs, warfarin (Coumadin®, Jantoven®), diuretics, rifampin, carbamazepine, phenytoin, quinidine, tramadol or fentanyl.Common side effects of TRINTELLIX include: nausea, constipation or vomiting. These are not all the possible side effects of TRINTELLIX.Do not start or stop taking TRINTELLIX without talking to your healthcare provider first. Suddenly stopping TRINTELLIX when you take higher doses may cause you to have side effects including headache, stiff muscles, mood swings, sudden outbursts of anger, dizziness or feeling lightheaded, or runny nose.Talk to your healthcare provider.You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Indication for TRINTELLIXTRINTELLIX is a prescription medicine used to treat Major Depressive Disorder (MDD) in adults.

Brintellix

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the label.

  • Hypersensitivity
  • Clinical Worsening and Suicide Risk
  • Serotonin Syndrome
  • Abnormal Bleeding
  • Activation of Mania/Hypomania
  • Hyponatremia

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.

Patient Exposure

BRINTELLIX was evaluated for safety in 4746 patients (18 years to 88 years of age) diagnosed with MDD who participated in pre-marketing clinical studies; 2616 of those patients were exposed to BRINTELLIX in 6 to 8 week, placebo-controlled studies at doses ranging from 5 mg to 20 mg once daily and 204 patients were exposed to BRINTELLIX in a 24 week to 64 week placebo-controlled maintenance study at doses of 5 mg to 10 mg once daily. Patients from the 6 to 8 week studies continued into 12-month open-label studies. A total of 2586 patients were exposed to at least one dose of BRINTELLIX in open-label studies, 1727 were exposed to BRINTELLIX for six months and 885 were exposed for at least one year.

Adverse Reactions Reported as Reasons for Discontinuation of Treatment

In pooled 6 to 8 week placebo-controlled studies the incidence of patients who received BRINTELLIX 5 mg/day, 10 mg/day, 15 mg/day and 20 mg/day and discontinued treatment because of an adverse reaction was 5%, 6%, 8% and 8%, respectively, compared to 4% of placebo-treated patients. Nausea was the most common adverse reaction reported as a reason for discontinuation.

Common Adverse Reactions in Placebo-Controlled MDD Studies

The most commonly observed adverse reactions in MDD patients treated with BRINTELLIX in 6 to 8 week placebo-controlled studies (incidence ≥ 5% and at least twice the rate of placebo) were nausea, constipation and vomiting.

Table 2 shows the incidence of common adverse reactions that occurred in ≥ 2% of MDD patients treated with any BRINTELLIX dose and at least 2% more frequently than in placebo-treated patients in the 6 to 8 week placebo-controlled studies.

Table 2: Common Adverse Reactions Occurring in ≥ 2% of Patients Treated with any BRINTELLIX Dose and at Least 2% Greater than the Incidence in Placebo-treated Patients

System Organ Class Preferred Term BRINTELLIX 5 mg/day
N=1013 %
BRINTELLIX 10 mg/day
N=699 %
BRINTELLIX 15 mg/day
N=449 %
BRINTELLIX 20 mg/day
N=455 %
Placebo
N=1621 %
Gastrointestinal disorders
Nausea 21 26 32 32 9
Diarrhea 7 7 10 7 6
Dry mouth 7 7 6 8 6
Constipation 3 5 6 6 3
Vomiting 3 5 6 6 1
Flatulence 1 3 2 1 1
Nervous system disorders
Dizziness 6 6 8 9 6
Psychiatric disorders
Abnormal dreams < 1 < 1 2 3 1
Skin and subcutaneous tissue disorders
Pruritus* 1 2 3 3 1
*includes pruritus generalized

Nausea

Nausea was the most common adverse reaction and its frequency was dose-related (Table 2). It was usually considered mild or moderate in intensity and the median duration was 2 weeks. Nausea was more common in females than males. Nausea most commonly occurred in the first week of BRINTELLIX treatment with 15 to 20% of patients experiencing nausea after 1 to 2 days of treatment. Approximately 10% of patients taking BRINTELLIX 10 mg/day to 20 mg/day had nausea at the end of the 6 to 8 week placebo-controlled studies.

Sexual Dysfunction

Difficulties in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of psychiatric disorders, but they may also be consequences of pharmacologic treatment.

In the MDD 6 to 8 week controlled trials of BRINTELLIX, voluntarily reported adverse reactions related to sexual dysfunction were captured as individual event terms. These event terms have been aggregated and the overall incidence was as follows. In male patients the overall incidence was 3%, 4%, 4%, 5% in BRINTELLIX 5 mg/day, 10 mg/day, 15 mg/day, 20 mg/day, respectively, compared to 2% in placebo. In female patients, the overall incidence was < 1%, 1%, < 1%, 2% in BRINTELLIX 5 mg/day, 10 mg/day, 15 mg/day, 20 mg/day, respectively, compared to < 1% in placebo.

Because voluntarily reported adverse sexual reactions are known to be underreported, in part because patients and physicians may be reluctant to discuss them, the Arizona Sexual Experiences Scale (ASEX), a validated measure designed to identify sexual side effects, was used prospectively in seven placebo-controlled trials. The ASEX scale includes five questions that pertain to the following aspects of sexual function: 1) sex drive, 2) ease of arousal, 3) ability to achieve erection (men) or lubrication (women), 4) ease of reaching orgasm, and 5) orgasm satisfaction.

The presence or absence of sexual dysfunction among patients entering clinical studies was based on their ASEX scores. For patients without sexual dysfunction at baseline (approximately 1/3 of the population across all treatment groups in each study), Table 3 shows the incidence of patients that developed treatment-emergent sexual dysfunction when treated with BRINTELLIX or placebo in any fixed dose group. Physicians should routinely inquire about possible sexual side effects.

Table 3: ASEX Incidence of Treatment Emergent Sexual Dysfunction*

BRINTELLIX 5 mg/day
N=65:67†
BRINTELLIX 10 mg/day
N=94:86†
BRINTELLIX 15 mg/day
N=57:67†
BRINTELLIX 20 mg/day
N=67:59†
Placebo
N=135:162†
Females 22% 23% 33% 34% 20%
Males 16% 20% 19% 29% 14%
*Incidence based on number of subjects with sexual dysfunction during the study / number of subjects without sexual dysfunction at baseline. Sexual dysfunction was defined as a subject scoring any of the following on the ASEX scale at two consecutive visits during the study: 1) total score ≥ 19; 2) any single item ≥ 5; 3) three or more items each with a score ≥ 4
†Sample size for each dose group is the number of patients (females:males) without sexual dysfunction at baseline

Adverse Reactions Following Abrupt Discontinuation of BRINTELLIX Treatment

Discontinuation symptoms have been prospectively evaluated in patients taking BRINTELLIX 10 mg/day, 15 mg/day, and 20 mg/day using the Discontinuation-Emergent Signs and Symptoms (DESS) scale in clinical trials. Some patients experienced discontinuation symptoms such as headache, muscle tension, mood swings, sudden outbursts of anger, dizziness, and runny nose in the first week of abrupt discontinuation of BRINTELLIX 15 mg/day and 20 mg/day.

Laboratory Tests

BRINTELLIX has not been associated with any clinically important changes in laboratory test parameters in serum chemistry (except sodium), hematology and urinalysis as measured in the 6 to 8 week placebo-controlled studies. Hyponatremia has been reported with the treatment of BRINTELLIX . In the 6-month, double-blind, placebo-controlled phase of a long-term study in patients who had responded to BRINTELLIX during the initial 12-week, open-label phase, there were no clinically important changes in lab test parameters between BRINTELLIX and placebo-treated patients.

Weight

BRINTELLIX had no significant effect on body weight as measured by the mean change from baseline in the 6 to 8 week placebo-controlled studies. In the 6-month, double-blind, placebo-controlled phase of a long-term study in patients who had responded to BRINTELLIX during the initial 12-week, open-label phase, there was no significant effect on body weight between BRINTELLIX and placebo-treated patients.

Vital Signs

BRINTELLIX has not been associated with any clinically significant effects on vital signs, including systolic and diastolic blood pressure and heart rate, as measured in placebo-controlled studies.

Other Adverse Reactions Observed in Clinical Studies

The following listing does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have significant clinical implications, or 5) which occurred at a rate equal to or less than placebo.

Ear and labyrinth disorders — vertigo

Gastrointestinal disorders — dyspepsia

Nervous system disorders — dysgeusia

Vascular disorders — flushing

Read the entire FDA prescribing information for Brintellix (Vortioxetine Tablets)

Trintellix (Vortioxetine) & Weight Gain or Weight Loss?

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Trintellix (Vortioxetine hydrobromide), formerly sold under the name Brintellix, is an antidepressant that was jointly developed by the pharmaceutical companies Lundbeck and Takeda. In 2013, Trintellix received FDA approval for the treatment of major depressive disorder in the United States. Trintellix is classified as a “serotonin modulator and stimulator” in that it functions as an inhibitor, antagonist, and agonist of various serotonin receptors.

More specifically, Trintellix inhibits the serotonin transporter (SERT); antagonizes 5-HT3 receptors; agonizes 5-HT1A receptors; and antagonizes 5-HT7 receptors. Through its unique serotonergic action, many users of Trintellix find that the drug alleviates depressive symptoms. However, some individuals are concerned with potential side effects of Trintellix, including body weight change (weight gain or weight loss).

Trintellix (Vortioxetine) & Weight Gain: Possible Causes

If you experience weight gain as a result of Trintellix, below are some potential causes. Understand that the specific causes of weight gain among Trintellix users (who end up gaining weight) will be subject to significant individual variation. Certain individuals might end up gaining weight because Trintellix increased their appetite (or reversed their poor appetite stemming from untreated major depressive disorder). Others might end up gaining weight because Trintellix slightly altered their hormones and/or metabolism.

  • Appetite increase: It is known that, for a subset of individuals, untreated depression results in low appetite which might lead to low caloric intake, weight loss, and a potentially an underweight BMI. In the event that you had untreated depression and weren’t consuming much food because the depression interfered with your appetite, you might find that Trintellix alleviates your depression, which in turn, normalizes your appetite. If your appetite normalizes (from a previously low appetite) while using Trintellix – you might consume more calories than you previously had been, and you may gain some weight. That said, even if you didn’t have a low appetite before Trintellix, there’s a chance that the medication could enhance your appetite – possibly causing weight gain.
  • Bloating: Most people won’t gain a significant amount of weight while using Trintellix. However, among those who notice weight gain from Trintellix, it’s possible that bloating (or water retention is the cause). Bloating may be related to changes in gut bacteria and/or gastrointestinal distress as a result of Trintellix treatment. If you suspect bloating as a cause of your weight gain, realize that it’s probably not actual “fat gain,” rather, a bit of extra water retention.
  • Blood sugar changes: Some individuals might experience blood sugar changes as a result of Trintellix. Though blood sugar changes aren’t known to be a common side effect, any medication that alters central serotonergic neurotransmission alter the hypothalamic-pituitary-adrenal axis, which in turn, affects insulin sensitivity. Deleterious changes to insulin sensitivity and/or blood glucose levels throughout treatment with Trintellix might increase your hunger and cause weight gain.
  • Constipation: A relatively common side effect of Trintellix is constipation, possibly resulting from decreased gastric motility. Constipation refers to difficulty emptying the bowels, and is usually associated with indigestion and hardened stools. If you’re regularly constipated and/or become severely constipated while using Trintellix, this might explain your weight gain. In other words, your body weight may be higher because you haven’t had a recent bowel movement.
  • Cravings: Some individuals taking Trintellix may notice an increase in cravings, particularly for unhealthy (hyperpalatable) foods, throughout their treatment. If you experience frequent or difficult-to-resist food cravings while taking Trintellix, the cravings might trigger you to eat more food (and total calories than usual), ultimately explaining your weight gain. Many people report increases in sugar and/or carbohydrates while taking antidepressants – this could somehow be related antidepressant-induced changes in serotonin signaling.
  • Fat storage: It’s possible that antidepressant medications like Trintellix could interact with hormones and/or genes implicated in fat storage to increase the amount of body fat that’s stored during treatment. Though there’s no direct evidence that Trintellix alters body composition via increasing body fat gain, it’s possible that Trintellix could trigger increased fat storage in a subset of Trintellix users, ultimately accounting for some weight gain.
  • Fatigue: As a result of the serotonergic modulation exerted by Trintellix, some individuals may experience increased fatigue or lethargy throughout treatment. If fatigue and/or lethargy is significant, this might lead to decreased physical activity and energy expenditure throughout the day. If Trintellix is making you tired or comfortably relaxed throughout the day to the point that you’ve become more sedentary than usual, this might account for any weight gain that you experience.
  • Gut bacteria: Taking Trintellix on a daily basis may negatively affect concentrations of gut bacteria or microbes. Any detrimental effects of Trintellix on gut bacteria could cause appetite increase, bloating, and even hormone changes – all of which may lead to weight gain. If you’re experiencing gastrointestinal distress or gastric side effects, there’s a chance that your gut bacteria were altered from Trintellix – possibly explaining some of your weight change.
  • Hormone changes: Trintellix and other antidepressant medications may interact with hormone production throughout the body, possibly increasing or decreasing certain hormones that regulate body weight. For example, many suspect that serotonergic antidepressants like SSRIs lower testosterone. If Trintellix is altering your body’s hormone production in an unfavorable way, you might lose some muscle and/or gain fat throughout treatment.
  • Lower motivation: Even if Trintellix treats your depression, you may end up with low motivation as a side effect. Some people using antidepressants report that the drugs make them feel emotionally numb and/or comfortably relaxed, such that they lack motivation to exercise or engage in physical activity. If your motivation plummets while using Trintellix and this yields lower physical activity throughout the day, this could explain your weight gain.
  • Social eating: Certain individuals with untreated depression isolate themselves from social events with others such as going out to eat. However, if depression is effectively treated with Trintellix, the persons who formerly isolated themselves may become more social – ultimately doing more social things, including, dining out. If you’re dining out more frequently since starting Trintellix, this may explain your weight gain. Although dining out more frequently doesn’t guarantee weight gain, it could increase likelihood of weight gain due to the fact that caloric loads (and portion sizes) are usually exceptionally large at restaurants (compared to home-cooked meals).
  • Slowed metabolism: As a result of changes in hormone production, gut bacteria, and physical activity while using Trintellix, you may end up with a slowed basal metabolic rate (BMR). A slowed BMR from Trintellix means that your body is burning fewer total calories (less energy) throughout the day than usual. Assuming Trintellix negatively affects your basal metabolic rate, this may be a reason as to why you’re gaining weight during treatment.
  • Taste enhancement: While taking Trintellix, you might notice that your taste improves or is enhanced compared to pre-treatment. In other words, foods end up tasting more delicious while using Trintellix compared to before using the drug. Taste enhancement while using Trintellix may result from Trintellix-induced neurochemical changes, connectivity changes, and/or regional activation changes within the brain. Assuming food ends up tasting better during treatment – you may have a difficult time putting down the fork.

Trintellix (Vortioxetine) & Weight Loss: Possible Causes

Although most people don’t end up experiencing significant weight change on Trintellix, a small percentage of individuals may report weight loss. Included below is a list of potential reasons as to why someone might lose weight while using Trintellix. Understand that the specific reasons that one Trintellix user loses weight during treatment may not be relevant to another.

  • Appetite reduction: Certain Trintellix users might notice that their appetite significantly decreases during treatment. Decreased appetite may be attributable to certain Trintellix side effects such as nausea and/or vomiting – let’s face it, it’s tough to eat food when you’re constantly nauseous. In other cases, decreased appetite may be due to the fact that a person’s depression is now properly treated. Some people exhibit heightened appetites with untreated depression, and when treated, appetite decreases back to normal. Regardless of why your appetite decreases on Trintellix, lower appetite usually results in decreased caloric intake – and weight loss.
  • Dehydration: If you experience a small amount of weight loss while using Trintellix, it may be explained by dehydration. Some individuals experience diarrhea and vomiting as side effects – each of which might lead to dehydration. If you’re dehydrated and weigh yourself, you may see that you lost a few pounds on the scale. That said, replenishing lost fluids by increasing water intake might get your weight back to normal.
  • Diarrhea: A common side effect of Trintellix is diarrhea, or the rapid passage of stools through the intestine. If you experience diarrhea, you may end up losing weight as a result of a laxative effect whereby your body isn’t absorbing the foods that you consume and excreting more water than usual. Once you get the diarrhea under control, you may notice that your body weight returns to normal.
  • Energy & motivation increase: Certain Trintellix users will report significant increases in physical energy and/or motivation – compared to pre-treatment. If your energy level and/or motivation increases as a result of Trintellix, you may be more likely to engage in physical exercise throughout the day. Assuming you’re exercising more while using Trintellix than before using it – you’ll likely end up losing weight.
  • Healthier food choices: When certain people are depressed, they may make unhealthy food choices such as eating hyperpalatable foods devoid of nutritional value (e.g. candies). Others with untreated depression may eat mostly fast-food because they’re too depressed or lack the energy to cook for themselves. If Trintellix effectively corrects depressive symptoms, individuals who formerly made unhealthy food choices (e.g. fast food) may start caring about their personal health and wellbeing whereby they make healthier food choices. Because healthier food choices are more satiating, those who eat healthier during treatment might consume fewer calories and lose some weight.
  • Metabolism increase: Some people may end up experiencing an increase in basal metabolic rate (BMR) while using Trintellix. An increase in BMR during treatment means that your body will be burning more calories than usual, possibly explaining your weight loss. Increased basal metabolic rate may be attributable to increased physical activity or exercise during Trintellix treatment (due to heightened motivation).
  • Nausea: A fairly common side effect of Trintellix is nausea. If you become nauseous throughout treatment with Trintellix, the thought of consuming food may be unappealing. Because nausea might lower appetite and lead to decreased caloric intake, those who experience nausea as a side effect of Trintellix may end up with weight loss. Getting the nausea under control will generally result in body weight normalization.
  • Self-control: Depression can sometimes interfere with self-regulation or self-control such that we have a difficult time restraining ourselves around food and end up overeating. However, when the depression is treated with an antidepressant medication like Trintellix, our self-control may increase. Better self-control means that you may have an easier time restraining yourself around food thereby minimizing likelihood of overeating.
  • Taste blunting: A very rare adverse effect of antidepressants like Trintellix is taste blunting. Taste blunting means that foods lack flavor and/or don’t taste as good as you remember. If you experience blunted taste while using Trintellix, you may not want to eat as much food – which could explain your weight loss.
  • Vomiting: In addition to nausea, some individuals using Trintellix may end up vomiting. Vomiting not only can cause dehydration, but it can prevent your body from absorbing foods that you recently consumed. For this reason, if you end up vomiting a lot during treatment, you could lose a bit of weight. Getting the vomiting under control should help get your body weight back to normal.

Trintellix & Body Weight Change (Research)

Included below are data trials in which the effect Trintellix (vortioxetine) on body weight was documented. Based on multiple reviews of the available drug data, it seems as though (for most users) Trintellix is unlikely to cause clinically significant weight gain or weight loss over the short-term and long-term.

2016: The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies.

Baldwin, Chrones, Florea, et al. analyzed data from randomized controlled trials and open-label extension studies in which vortioxetine (Trintellix) was administered. In the analysis, researchers documented the effect of Trintellix on participants’ body weights. As you’ll read, there didn’t appear to be any significant weight changes over the short-term (6-8 weeks) or long-term (up to 52 weeks) among Trintellix users – regardless of the dosage.

Short-term: Short-term trial data included 3018 adult patients treated with vortioxetine (5-20 mg per day) and 1817 patients treated with a placebo. It was discovered that short-term treatment with Trintellix (6-8 weeks) resulted in no clinically significant body weight change compared to a placebo. Results discovered that placebo users exhibited ~0.1 kg weight gain whereas vortioxetine users exhibited weight changes of -0.1 kg to +0.1 kg (with no dose-dependent effect). It was noted that the incidence of clinically relevant weight gain (defined as at least 7% weight increase from baseline) was: 0% (15 mg users); 1.2% (10 mg users); and 0.6% for placebo users. The incidence of clinically significant weight loss (defined as at least 7% weight decrease from baseline) was: 0.2% (5 mg users); 1.3% (20 mg users); and 0.6% for placebo users.

Long-term: Long-term trial data was extracted from 5 extension studies in which 1313 patients were treated with 5-10 mg vortioxetine (52 weeks) and 1144 patients were treated with 15-20 mg vortioxetine (51 weeks). At trial endpoints, average weight change from baseline among participants was +0.8 kg (5-10 mg) and +0.7 kg (15-20 mg). If converted from kg to lbs., this would equal +1.76 lbs. for 5-10 mg users and +1.54 lbs. for 15-20 mg users. The incidence of clinically significant weight gain (defined as 7% body weight increase from baseline) was 13.3% of the 5-10 mg users and 11% of the 15-20 mg users. The incidence of clinically significant weight loss (defined as 7% body weight decrease from baseline was 6.1% of the 5-10 mg users and 7.7% of the 15-20 mg users.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/26864543

2015: Profile of vortioxetine in the treatment of major depressive disorder: an overview of the primary and secondary literature.

Kelliny, Croarkin, Moore, and Bobo reported upon the effect of vortioxetine in the treatment of major depressive disorder. In their report, researchers noted that vortioxetine treatment was not associated with clinically significant changes in body weight among adults with major depressive disorder – when administered over a short-term of 6 to 8 weeks. Moreover, in a pooled analysis of short-term vortioxetine trials, clinically significant weight gain (or an increase of body weight by at least 7% from baseline) occurred in less than 3% of patients receiving vortioxetine at dosages within the range of 1 mg to 10 mg per day.

In long-term studies (~52 weeks), body weight change among vortioxetine users was modest (0.7-1.1 kg) and not clinically significant. Researchers concluded that vortioxetine doesn’t appear to be associated with clinically significant changes in body weight.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/26316764

Based on the research, how much weight change will most Trintellix users likely experience?

Nothing significant. The available short-term and long-term data from trials in which vortioxetine was administered to adults for the treatment of major depressive disorder reported no clinically significant weight changes among most users. This considered, it is reasonable to suggest that most Trintellix users are unlikely to experience significant changes in body weight over a short-term (6 to 8 weeks) and long-term (up to ~1 year). While it is possible that very long-term treatment (e.g. several years) might yield a different effect upon body weight than just ~1 year, this hypothesis isn’t substantiated by evidence.

  • Short-term users: Over the short-term of 6-8 weeks, vortioxetine users exhibit weight changes of -0.1 kg to +0.1 kg (regardless of the dose). In other words, most vortioxetine users might see their weight fluctuate by 0.22 lbs. (increase or decrease). How likely is clinically significant weight change (defined as 7% body weight increase or decrease) over the short-term? Less than 1.3% of users experience clinically relevant body weight change with short-term vortioxetine use.
  • Long-term users: Over a long-term of ~52 weeks, vortioxetine users exhibit an average weight change of +0.7 to +0.8 kg. In other words, most vortioxetine users might see their weight increase modestly (1.54 lbs. to 1.76 lbs.) over the span of 1 year. How likely is clinically significant weight change (defined as 7% body weight increase or decrease) over the long-term? Clinically significant weight gain may occur in 11-13% of long-term vortioxetine users, whereas clinically significant weight loss may occur in ~7.7% of long-term vortioxetine users.

Variables that influence Trintellix (Vortioxetine) weight change

There are several variables that may influence the amount of weight change (gain or loss) that you experience while using Trintellix. These variables include: prior substance use; genetics; lifestyle; concurrent substance use; duration of treatment; and Trintellix dosage. It is the combination of these variables that likely determine which Trintellix users experience weight change – as well as its significance.

  1. Prior medication use: If you used antidepressant medications before Trintellix, there’s a chance that those medications may have caused weight gain or weight loss. If you took a medication that made you gain weight (prior to Trintellix), you may end up losing weight when you switch to Trintellix. Oppositely, if you took a medication that made you lose weight (prior to Trintellix), you may end up gaining weight while using Trintellix. In these cases, the weight gain and/or loss experienced after switching Trintellix will largely be due to homeostatic rebound effects (opposite of what was experienced on the prior medication).
  2. Genetics: Individuals who gain or lose a significant amount of weight while taking Trintellix may have genetics that differ from the majority of the population. For example, someone might have genetics that interact with Trintellix in a way that increases appetite or fat storage to a significantly greater extent than other users. Though the specific ways in which genetics interact with Trintellix aren’t fully known, drug-gene weight interactions are likely.
  3. Lifestyle: Your lifestyle may also determine whether you’re prone to experiencing significant weight change while using Trintellix. If you aren’t getting adequate sleep, are highly stressed, are sedentary, and/or eat unhealthy foods – this may be a recipe for weight gain, regardless of the medication you’re using. On the other hand, if you’re getting enough sleep, keeping stress low, are active, and eat healthy – you may end up losing weight during treatment.
  4. Concurrent substances: If you’re taking other medications or substances with Trintellix, there’s a chance that this may influence the weight change that you experience on Trintellix. First you must consider that the concurrent substances that you’re using may be causing weight change instead of Trintellix. Then you must consider that there could be neurotransmitter-mediated, hormonally-mediated, and/or metabolism-mediated interactions (CYP450) between Trintellix and the other substance(s) that would explain weight change.
  5. Duration of treatment: Some individuals may experience weight changes after a short-term followed by weight stabilization, whereas others might experience no weight changes over a short-term followed by significant weight change over a long-term. In any regard, the total duration over which you’ve used Trintellix may influence how much weight you gain or lose.
  6. Trintellix dosage: Research suggests that there aren’t clinically significant effects of Trintellix dosage on body weight among users. That said, there may be individual variation in responses to dose on body weight. Some individuals may experience a stronger weight loss or weight gain effect at a higher dose – than a lower dose. Others might experience weight loss at a higher dose and weight gain at a lower dose.

Possible ways to minimize weight change on Trintellix (Vortioxetine)

Most people will not experience significant body weight changes while using Trintellix. That said, if you are experiencing weight change (weight gain or weight loss) from Trintellix, below are some possible ways to minimize the unwanted weight change. Realize that you should never implement any of these strategies without first consulting a medical professional to ensure that they’re safe.

  1. Track calories & activity: One thing many people don’t do is track their calories and record their physical activity. Tracking your calories and physical activity each day will help you understand whether you should be gaining, losing, or maintaining weight. Most people can prevent significant weight gain or weight loss by eating maintenance calories.
  2. Manage side effects: Certain side effects like nausea, diarrhea, and vomiting can cause weight loss. Other side effects such as fatigue could cause weight gain in some cases. If your side effects from Trintellix are culpable for your weight changes, it may help to get the side effects under control. Once you’ve controlled your side effects, your weight may normalize.
  3. Dosage modification: Sometimes modifying your dosage of Trintellix may decrease weight change throughout treatment. Using the “minimal effective dose” will reduce the effect of Trintellix on your physiology which should lower likelihood of clinically relevant weight change attributable to the medication.
  4. Consider concurrent medications: If you’re experiencing unwanted weight change, you may want to evaluate the concurrent medications and/or substances that you use. Eliminating all medically-unnecessary substances that you’re using with Trintellix may help you get your weight recover to normal. That said, adding concurrent medications (that are recommended by a psychiatrist) to be taken with Trintellix might also help keep your weight within a healthy range.
  5. Use for a longer-term: Certain Trintellix users get caught up in their weight change over a short-term. Because weight can fluctuate as the body adjusts to the medication (over a short-term), using Trintellix for a longer-term span may help you get a more accurate understanding of how it affects your weight.

Note: If you’re still unhappy with Trintellix weight gain or weight loss and nothing seems to help you get your weight back on track, you may want to talk to your doctor about Trintellix withdrawal and/or switching to another medication. Although Trintellix stays in your system for a bit of time after discontinuation, your weight should gradually begin normalizing (over a period of weeks) once it has been eliminated.

Have you experienced weight changes on Trintellix?

If you’ve experienced weight gain or weight loss from Trintellix, leave a comment below. In your comment, mention how much weight you gained or lost while using Trintellix. Also note things like: how quickly you noticed the weight change (after starting treatment) and whether the weight change worsened, reversed, or self-corrected over a longer-term. To help others get a better understanding of your situation, provide details such as: your Trintellix dosage; duration of Trintellix use; whether you use other substances (meds or supplements) with Trintellix; and note whether you’ve tracked your calories and physical activity throughout treatment.

17 Shares

Their antidepressant is expensive, and it isn’t selling well.

But the drug makers behind the medication are betting they can give it a boost by marketing it to treat a whole new category of depression symptoms — namely, cloudy thinking.

The catch: The Food and Drug Administration must first be persuaded that such symptoms can be treated as a separate category — and that the drug, sold as Brintellix, can treat it.

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An FDA advisory committee meets Wednesday morning to debate whether cognitive dysfunction can be pulled out and treated as “a distinct entity,” separate from symptoms like pervasive sadness and apathy. That will set the stage for an afternoon vote on whether the FDA should approve Brintellix as the first treatment for the muddled thinking that often comes along with depression.

Drug makers Takeda Pharmaceuticals and Lundbeck are counting on approvals to create new demand for the drug and new justification to convince insurance companies to pay for it.

But experts say it’s not clear that Brintellix is any more effective than its competitors in making a difference for reversing depression’s cognitive complications.

“Clinically, in talking to my colleagues, we don’t really see any major differences in terms of cognitive effects between Brintellix and other drugs,” said Dr. Norman Sussman, a psychiatrist at New York University’s Langone Medical Center. “We don’t know that Prozac doesn’t do it as well. Or Zoloft. Or any of the other drugs.”

Brintellix, known generically as vortioxetine, was approved in 2013 for treating depression. And in a field dominated by generics, Brintellix stands out mostly for the hefty price tag it carries.

A 30-tablet regimen of the drug went for $290 late last year. Compare that with equivalent dosages of the many off-patent alternatives on the market: a generic version of Prozac sold by Vensun Pharmaceuticals has a $3 price tag, and a generic version of Zoloft sold by Northstar Rx goes for $5. (Those numbers, compiled by the research firm Truven Health Analytics, refer to the price that a manufacturer listed for a drug when it was sold to a wholesaler.)

That price gap has prompted health plans to balk when physicians try to prescribe Brintellix.

Clinicians often face a headache of paperwork demands from insurance companies when seeking justification for a Brintellix prescription, and many plans have formal policies in place to limit them. For example, the Michigan insurer HealthPlus will only cover Brintellix for patients who’ve struggled with dosage levels and have already tried at least three generic antidepressants.

That’s made many psychiatrists reluctant to prescribe Brintellix, or prompted them to only turn to it as a late resort for patients for whom other cheaper drugs have failed.

“I don’t want to start someone on something and know that they’re not going to be able to afford more than a week of it,” said Dr. Christopher Marano, a psychiatrist at Johns Hopkins University School of Medicine who specializes in treating depression in the elderly. “From my perspective, I don’t see any reason to jump right to Brintellix as a first-line agent right now.”

Takeda and Lundbeck’s investment in research to show that Brintellix can effectively treat the cognitive symptoms of depression — including problems with concentration, memory, and processing speed — is an effort to change that attitude among doctors.

Brintellix is angling to become the first drug approved for the treatment of cognitive symptoms caused by depression. Courtesy Takeda

Like all antidepressants on the market, Brintellix initially won FDA clearance on the back of studies that focused on mood-related symptoms. But Takeda and Lundbeck also ran two trials looking specifically at cognitive symptoms in patients who took the drug compared to those who took a placebo.

The results of those trials, which involved a total of 1,200 patients with moderate to severe depression, will be under the microscope when the FDA panel of mental health advisors meets this week at the agency’s White Oak Campus in Silver Spring, Md. The FDA doesn’t have to follow the panel’s recommendations, but it usually does. The agency has a deadline of March 28 to make a final decision on the expanded marketing application.

Takeda and Lundeck’s strategy follows a familiar playbook: Drug makers often try to boost sales of existing medications by looking for new indications that could help them stand out from the crowd. (Another typical approach, particularly for companies in the antidepressant market, is to invest in research to make the case that their drug causes fewer side effects than competitors.)

Brintellix appears to provide cognitive benefits, but anecdotal reports suggest that other antidepressants do, too.

But patients with depression and their doctors don’t have a good way to assess whether Brintellix is their best option because no trials — including the ones being used to support Brintellix’s application — have tested drugs head-to-head for their cognitive effects. And the makers of antidepressants that have gone generic have little incentive to invest in the kinds of rigorous clinical studies needed for FDA approval.

Dr. Roger McIntyre, a psychiatrist at the University of Toronto who led one of the trials supporting Brintellix’s FDA application, acknowledged that the lack of direct comparisons was a limitation. But he said he has other reasons to be optimistic about the drug.

Unlike many other antidepressants, which just block the reuptake of serotonin and other neurotransmitters, Brintellix can modulate the proteins that seratonin switches on, a mode of action which has downstream effects on other neurochemical systems. And compared to other antidepressants, Brintellix has more consistently spurred neuronal connections in brain cells when tested in a laboratory setting.

“We do have pieces of the puzzle that provide a robust scientific rationale that would lead us to believe that there’s something unique about this agent at the neurochemical level in the brain,” said McIntyre, who accepts consulting fees, speaking fees, and research support from Takeda, Lundbeck, and some of their competitors.

Neither Takeda nor Lundbeck made an executive available for an interview.

Clinically superior to its competitors or not, a new marketing authorization from the FDA would give Takeda and Lundbeck the ability to advertise Brintellix for that purpose, and to dispatch sales representatives to doctors’ offices to tout that use. Those factors would likely boost prescriptions by psychiatrists looking to help patients with cognitive symptoms — and make it harder for insurers to say no.

“The ammunition will be much stronger for clinicians if there’s a label that supports this drug being different from the others,” said Harry Tracy, a pharmaceutical industry consultant and the publisher of NeuroPerspective, a bimonthly publication focused on treatments for neurological and psychiatric diseases.

But first, the advisory committee that meets Wednesday must be convinced not only that Brintellix works, but also that cognitive dysfunction in depression can even be treated in the first place.

It’s hardly a given. There’s no clear view about how to diagnose depression-induced cognitive dysfunction, or what to measure in designing trials testing drugs that might be able to treat it.

But many patients and their families clearly see an unmet need.

Gary Girton, who suffered from severe depression for most of his life, found relief for years by working in his studio as a mosaic artist. Yet, as the cognitive symptoms of his depression intensified in the last year and a half of his life, it became harder for him to do what he loved.

Remembering where he’d left off on a project, distinguishing spacial elements, and being creative all became more frustrating until he stopped going to his studio. He died by suicide in 2014, at the age of 45.

His widower, Marlin Collingwood, now the executive director of the Massachusetts-based nonprofit Families for Depression Awareness, submitted written testimony that will be considered on Wednesday advocating for greater focus on the cognitive symptoms. (Girton never took Brintellix, and Collingwood won’t take a position on its application.)

“The fact that the FDA and pharma companies are seriously looking at ways to help those people deal with the cognitive side of things” Collingwood said, “is a very important step forward in the treatment of depression.”

Vortioxetine (Brintellix) for the Treatment of Depression

SAFETY

The safety profile of vortioxetine is similar to that of other selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. As with other antidepressants in this class, vortioxetine includes a black box warning of increased risk of suicidal thoughts and behavior in children, adolescents, and young adults. It may also cause clinical worsening or activation of mania or hypomania.2 However, current data show no increase in suicidality in the first year of use.3 Vortioxetine should not be used with monoamine oxidase inhibitors, linezolid (Zyvox), intravenous methylene blue, or other serotonergic drugs because of the risk of serotonin syndrome. Vortioxetine may increase the risk of bleeding events, particularly when taken with nonsteroidal anti-inflammatory drugs or other medications that affect coagulation. It also may cause hyponatremia, which is rare but can be severe. This is more likely to happen in older adults, persons taking diuretics, and those who are volume depleted. Vortioxetine is a U.S. Food and Drug Administration pregnancy category C drug.2

TOLERABILITY

Vortioxetine is generally well tolerated. The dropout rate from side effects in the first year of use is 6%. Vortioxetine is not associated with significant weight gain over at least one year of treatment.3 Nausea is the most common side effect, occurring in up to 38% of patients, and is usually temporary and reported as mild to moderate. Headache occurs in up to 25% of patients. Other common side effects include dizziness, dry mouth, nasopharyngitis, and diarrhea; these generally occur in less than 10% of patients.1,3–9 Sexual dysfunction rates with vortioxetine are similar to those with duloxetine (Cymbalta).8,9 Lower doses of vortioxetine produced less sexual dysfunction than did higher doses of venlafaxine; the two medications have not been compared at pharmacologically equivalent doses.4

EFFECTIVENESS

Similar to other antidepressants in this class, the antidepressant effect of vortioxetine begins after about two weeks of treatment, reaching full effect at four weeks or beyond. There is no significant difference in effectiveness between the typical starting dosages of 5 and 10 mg per day; however, a higher dosage of 20 mg per day is more effective than lower dosages. Vortioxetine has not been studied in patients with mild to moderate depression; in patients with moderate to severe depression, outcome data are mixed. About 50% to 70% of patients will respond to treatment, defined as a 50% reduction in depression score (based on results of the Montgomery-Åsberg Depression Rating Scale and the 17- and 24-item Hamilton Depression Rating Scales).4,6,8 Remission occurs in about 20% to 60% of patients,4,6,8 and it is maintained in about 62% of patients at 52 weeks.3 Vortioxetine may also prevent relapse at 24 weeks.1 However, at least three studies have shown no benefit of vortioxetine over placebo.5,7,9 Comparative data show no benefit of vortioxetine over other antidepressants, but these trials compared lower dosages of vortioxetine (10 mg per day or less) to maximal dosages of venlafaxine (225 mg per day) and duloxetine (60 mg per day).4,5,8,9

PRICE

A one-month supply of vortioxetine (5 mg or 10 mg per day) costs approximately $254. In comparison, a one-month supply of duloxetine (60 mg per day) costs approximately $35, and a one-month supply of venlafaxine (75 mg per day) costs approximately $15. Fluoxetine and amitriptyline are each available for $4 for a one-month supply.

SIMPLICITY

Vortioxetine is taken once daily without regard to meals. The starting dosage is 5 or 10 mg per day and can be titrated to a maximal dosage of 20 mg once daily. Although vortioxetine can be discontinued abruptly, it is recommended that higher dosages of 15 or 20 mg per day be reduced to 10 mg per day for one week before full discontinuation to avoid adverse reactions.2

Choose region and then country

Below is a copy of the content of the Consumer Medicine Information Leaflet provide with the Brintellix® medicine.

Brintellix®

Vortioxetine hydrobromide (vor-tee-ox-e-teen high-dro-bro-mide)

Consumer Medicine Information

What is in this leaflet

This leaflet answers some common questions about Brintellix. It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Brintellix against the benefits they expect it will have for you.

If you have any concerns about taking this medicine ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What Brintellix is used for

Brintellix contains vortioxetine, which is used to treat major depression in adults.

Depression is longer lasting or more severe than the “low moods” everyone has from time to time due to the stress of everyday life. It is thought to be caused by a chemical imbalance in parts of the brain. This imbalance affects your whole body and can cause emotional, physical and cognitive symptoms such as feeling low in spirit, reduced ability to think or concentrate, or indecisiveness, loss of interest in activities, being unable to enjoy life, poor appetite or overeating, disturbed sleep, often waking up early, loss of sex drive, lack of energy and feeling guilty over nothing.

Brintellix is thought to work by its actions on multiple brain chemicals including serotonin, noradrenaline, dopamine, histamine and acetylcholine which are thought to be involved in controlling mood and related mental processes.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

Brintellix is available only with a doctor’s prescription.

Brintellix is not addictive.

Brintellix should not be given to children under 18 years of age.

Before you take Brintellix

When you must not take it

Do not take Brintellix if you have an allergy to:

  • vortioxetine
  • any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

Do not take Brintellix at the same time as the following other medicines:

  • monoamine oxidase inhibitors (MAOIs), such as phenelzine, tranylcypromine, selegiline, rasagiline and moclobemide
  • medicines which act like a monoamine oxidase inhibitor, such as the antibiotic linezolid

Taking Brintellix with MAOIs may cause a serious reaction including sudden changes in mental state, twitching, rapid heartbeat, high blood pressure, fever and diarrhoea.

If you have taken an MAOI, you will need to wait at least 14 days before starting Brintellix. If you have used moclobemide, one day must elapse after you stop taking moclobemide before you start taking Brintellix.

After stopping Brintellix, you must allow at least 14 days before taking any MAOI or moclobemide.

Do not take Brintellix after the expiry date (EXP) printed on the pack. The expiry date refers to the last day of the month.

It may have no effect at all or, an entirely unexpected effect if you take it after the expiry date.

Do not take Brintellix if the packaging is torn or shows signs of having been tampered with.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you are pregnant or plan to become pregnant.

Brintellix should not be used during pregnancy unless the benefit outweighs the risk. Your doctor can discuss with you the risks and benefits involved.

When taken during pregnancy, particularly in the last three months of pregnancy, medicines like Brintellix may increase the risk of a serious condition in babies called persistent pulmonary hypertension of the newborn (PPHN), making the baby breathe faster and appear bluish. These symptoms usually begin during the first 24 hours after the baby is born.

Other effects on your baby may include difficulty breathing, fits, body temperature changes, feeding difficulties, vomiting, stiff or floppy muscles, tremor, jitteriness, irritability, lethargy, constant crying, sleepiness or sleeping difficulties.

If your newborn baby has any of the above symptoms, you should contact your doctor immediately.

Tell your doctor if you are breastfeeding or planning to breast-feed

It is recommended that you do not breast-feed while taking Brintellix, as it may be excreted in the milk.

Tell your doctor if you have, or have had, the following medical conditions:

  • A tendency to bleed or bruise easily
  • Low sodium levels in the blood
  • Seizures or fits
  • A history of suicide-related events or suicidal ideas
  • A history, or family history, of mania or bipolar disorder (manic depression)
  • Other diseases affecting the brain, including psychiatric conditions
  • Other significant medical illnesses, such as unstable heart disease, stroke or severe liver or kidney disease

Tell your doctor if are 65 years of age or older.

Tell your doctor if you are receiving electroconvulsive therapy.

Do not give Brintellix to a child or adolescent.

There is no experience with the use of Brintellix in children or adolescents less than 18 years of age.

If you have not told your doctor about any of the above, tell them before you use Brintellix.

Ask your doctor or pharmacist for advice before taking any medicine.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines and Brintellix may interfere with each other. These include:

  • Monoamine oxidase inhibitors (MAOIs), including selegiline, rasagiline, linezolid and moclobemide.

You must stop taking MAOIs at least two weeks before starting Brintellix. You must wait at least one day after finishing moclobemide before you start Brintellix.

You must stop taking Brintellix at least two weeks before you start taking an MAOI or moclobemide.

  • rifampicin, an antibiotic
  • St. John’s Wort, a herbal remedy
  • sumatriptan (and similar medicines ending in ‘triptan’), medicines used to treat migraine headaches
  • lithium, used to treat mood swings and some types of depression
  • tryptophan, an amino acid
  • tramadol, used to relieve pain
  • mefloquine, an anti-malaria medicine
  • bupropion, a medicine for nicotine dependence
  • medicines known to cause low sodium level in the blood
  • medicines used to thin the blood or known to prolong bleeding e.g. warfarin, dipyridamole, aspirin, and non-steroidal antiinflammatory drugs (NSAIDs)
  • antipsychotics, a class of medicines used to treat mental illness, e.g. risperidone, olanzapine, quetiapine
  • tricyclic antidepressants, e.g.imipramine, desipramine
  • any other medicines for depression, anxiety, panic disorder, obsessive-compulsive disorder or pre-menstrual dysphoric disorder

These medicines may be affected by Brintellix, or may affect how well it works. You may need to use different amounts of medicines, or take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

If you have not told your doctor or pharmacist about any of these things, tell them before you take Brintellix.

How to take Brintellix

Follow all directions given to you by your doctor or pharmacist carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions on the label, ask your doctor or pharmacist for help.

How much to take

Your doctor will tell you how much Brintellix to take each day. Take the amount your doctor tells you to.

The usual dose for Brintellix in adults less than 65 years of age is 10 mg taken orally as one daily dose. The dose may be increased by your doctor to a maximum of 20 mg per day or lowered to a minimum of 5 mg per day.

For elderly people 65 years of age or older, the starting dose is 5 mg taken once daily.

Ask your doctor or pharmacist if you are unsure of the correct dose for you.

They will tell you exactly how much to take.

Follow the instructions they give you.

If you take the wrong dose, Brintellix may not work as well and your condition may not improve.

How to take it

Swallow the tablets whole with a full glass of water.

When to take it

Take Brintellix as a single dose either in the morning or in the evening.

Take your medicine at about the same time each day.

It does not matter if you take Brintellix before or after food.

How long to take it

Continue to take Brintellix even if it takes some time before you feel any improvement in your condition.

It may take two weeks, sometimes longer, before you feel any improvement.

Continue to take Brintellix for as long as your doctor recommends.

If your depression resolves while taking BRINTELLIX treatment should be continued for at least 6 months after you feel well again.

Your doctor will check your progress at regular intervals.

Do not change the dose or stop taking this medicine without first checking with your doctor.

If you forget to take it

Take the next dose at the usual time.

Do not take a double dose to make up for the dose that you missed.

This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (Telephone 13 11 26) for advice, or go to the Accident and Emergency department at your nearest hospital if you think that you or anyone else may have taken too much Brintellix. Take the Brintellix container with you when you go to the hospital. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Keep the telephone number handy.

Some of the signs of an overdose could be dizziness, feeling sick (nausea), diarrhoea, stomach discomfort, itching on the whole body, sleepiness and flushing.

While you are taking Brintellix

Things you must do

Tell your doctor immediately if you become pregnant while taking Brintellix.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Brintellix.

Tell all doctors, dentists and pharmacists who are treating you that you are taking Brintellix.

Keep all of your doctor’s appointments so that your progress can be checked.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking Brintellix.

It may affect other medicines used during surgery.

If you have thoughts about killing yourself or other mental/mood changes, contact your doctor immediately or go to the nearest hospital for treatment.

All mentions of suicide or violence must be taken seriously.

Occasionally, the symptoms of depression may include thoughts of suicide or self-harm. It is possible that these symptoms continue or get worse until the full antidepressant effect of the medicine becomes apparent.

This is more likely to occur:

  • if you are a young adult, i.e. 18 to 24 years of age; or
  • you have previously had thoughts about killing or harming yourself

You may find it helpful to tell a relative or close friend that you are depressed and ask them to read this leaflet. You might ask them to tell you if they think your depression is getting worse, or if they are worried about changes in your behaviour.

Patients and care givers should pay attention for any of the following warning signs of suicide-related behaviour while taking Brintellix:

  • worsening of depression
  • thoughts or talk of death or suicide
  • thoughts or talk of self-harm or harm to others
  • any recent attempts of self-harm
  • increase in aggressive behaviour, irritability, agitation or any other unusual changes in behaviour or mood.

Things you must not do

Do not take Brintellix to treat any other complaints unless your doctor tells you to.

Do not give Brintellix to anyone else, even if they have the same condition as you.

Do not stop taking Brintellix, or lower the dosage, without checking with your doctor.

If you stop taking it suddenly, or reduce the amount you take, your condition may worsen.

Things to be careful of

Be careful driving or operating machinery until you know how Brintellix affects you.

Avoid alcohol while you are taking Brintellix.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Brintellix.

Brintellix helps most people with depression, but it may have unwanted side effects in some people.

All medicines can have side effects.

Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following side effects and they worry you:

  • feeling sick (nausea)
  • diarrhoea or constipation
  • vomiting
  • influenza type symptoms
  • decreased appetite
  • sedation
  • itching on the whole body

The above list includes the more common side effects of your medicine.

Side effects are generally mild to moderate and occur within the first two weeks of treatment. They are usually temporary and generally do not require treatment cessation.

Tell your doctor as soon as possible if you notice any of the following:

  • mania* (symptoms include mood of excitement, over-activity and uninhibited behaviour)
  • low sodium levels in the blood* (symptoms include feeling tired, weak and sick with weak muscles or feeling confused)
  • bleeding tendency* (e.g. bruising)

The above list includes serious side that may require medical attention.

Tell your doctor immediately, or go to Accident and Emergency at your nearest hospital, if you notice any of the following:

  • Thoughts of harming yourself or thoughts of suicide, see also section “Things you must do”*
  • serious allergic reaction (symptoms of an allergic reaction may include swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing, or rash, itching or hives)
  • high fever, agitation, confusion, trembling and abrupt contractions of muscles

(these symptoms may be signs of a rare condition called serotonin syndrome)*

  • seizures*
  • bleeding* (e.g. vomiting of blood, traces of blood in your stools or your stools are dark in colour)

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

* The side effects marked with an asterisk (*) are a number of rare side effects that are known to occur with medicines that work in a similar way to Brintellix.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After taking Brintellix

Storage

Keep Brintellix in the blister pack until it is time to take them.

If you take the tablets out of the box or blister pack they may not keep well.

Keep Brintellix in a cool dry place where the temperature stays below 30°C.

Do not store Brintellix or any other medicine in the bathroom or near a sink or stove. Do not leave it on a window sill or in the car.

Heat and dampness can destroy some medicines.

Keep Brintellix where young children cannot reach it.

A locked cupboard at least one-and a-half metres above ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine you may have left over.

Brintellix description

What Brintellix tablets look like

  • Brintellix 5 mg tablets are pink, almond-shaped, biconvex filmcoated tablet engraved with “TL” on one side and “5” on the other side.
  • Brintellix 10 mg tablets are yellow, almond-shaped, biconvex film-coated tablet engraved with “TL” on one side and “10” on the other side.
  • Brintellix 15 mg tablets are orange, almond-shaped, biconvex film-coated tablet engraved with “TL” on one side and “15” on the other side.
  • Brintellix 20 mg tablets are red, almond-shaped, biconvex filmcoated tablet engraved with “TL” on one side and “20” on the other side.

Brintellix is available in blister packs of 28 tablets

Ingredients
Active ingredients

  • Brintellix 5 mg tablets contain 5 mg vortioxetine (as hydrobromide) per tablet
  • Brintellix 10 mg tablets contain 10 mg vortioxetine (as hydrobromide) per tablet
  • Brintellix 15 mg tablets contain 15 mg vortioxetine (as hydrobromide) per tablet
  • Brintellix 20 mg tablets contain 20 mg vortioxetine (as hydrobromide) per tablet

Brintellix also contains:

  • Mannitol
  • Microcrystalline cellulose
  • Hydroxypropylcellulose
  • Sodium starch glycollate type A
  • Magnesium stearate
  • Hypromellose
  • Titanium dioxide
  • Macrogol 400
  • Iron oxide red CI 77491 (5, 15 and 20 mg tablets)
  • Iron oxide yellow CI 77492 (10 and 15 mg tablets)

Brintellix does not contain lactose, gluten, sucrose, tartrazine or any other azo dyes.

Manufacturer and distributor

Brintellix is made by H. Lundbeck A/S, Denmark.

Distributed in Australia by:
Lundbeck Australia Pty Ltd
1 Innovation Road
North Ryde NSW 2113
Ph: 02 8669 1000

This leaflet was prepared on 5 March 2014.

Australian Registration Numbers are:
5 mg tablet: AUST R 203986
10 mg tablet: AUST R 203955
15 mg tablet: AUST R 203981
20 mg tablet: AUST R 203970

Brintellix is a registered trade mark of H. Lundbeck A/S.
Copyright© 2014 H. Lundbeck A/S
AU-6594-CMI

The efficacy and safety of multiple doses of vortioxetine for generalized anxiety disorder: a meta-analysis

Introduction

Generalized anxiety disorder (GAD) is a common mental disorder marked by persistent anxiety and worries as well as multiple psychological and physical symptoms.1 GAD is a burden on the society because it is costly and has a significant adverse effect on the quality of life.2 The serotonin (5-hydroxytryptamine ) transporter, 5-HT receptors, are promising therapeutic targets for treating GAD, and currently most psychiatrists prefer the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs).3 In addition, the recent guidelines suggest SSRI/SNRI as the first-line pharmacotherapy for GAD.4,5 Vortioxetine is a multimodal antidepressant approved for the treatment of major depressive disorder (MDD) by the US Food and Drug Administration in September 2013. The mechanism of action of vortioxetine is thought to be a combination of two pharmacological modes of action: the direct modulation of receptor activity and the inhibition of the serotonin transporter. In vitro studies indicate that vortioxetine functions as a 5-HT3 and 5-HT7 receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist, and an inhibitor of the 5-HT transporter.6,7 Several meta-analyses have proved the efficacy of vortioxetine in the treatment of MDD,8–10 and one of them is our work.10 The symptoms of anxiety and depression respond to similar agents, suggesting that the two conditions share some common neuropathology. However, the antianxiety effect of vortioxetine in treating GAD is uncertain. One recent study conducted by Pae et al11 suggests that vortioxetine may have a potential as an another treatment option for GAD. Based on the newest available data, we conducted a meta-analysis to assess the efficacy and safety of multiple doses of vortioxetine in the treatment of GAD in adults.

Methods

Literature search

PubMed, Cochrane Library, PsycINFO, and the Clinical Trials databases (from 2000 through 2015) were searched using the keywords “vortioxetine OR LuAA21004 OR Brintellix” AND “anxiety OR anxiety disorder OR mood disorder”. The abstracts of the annual meetings of the American Psychiatric Association and previous reviews were also searched to identify additional trials. The search was limited to individual randomized controlled trials (RCTs) and there was no language restriction.

Trial selection

Trials that met the following criteria were included: parallel group, double-blind, placebo-controlled with random assignment, and patients (≥18 years old) primarily diagnosed with GAD according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revised (DSM-IV-TR). Patients who were included had a Hamilton Anxiety Rating Scale (HAM-A) total score ≥20 and a HAM-A score ≥2 on both item 1 (anxious mood) and item 2 (tension), and a Montgomery–Åsberg Depression Rating Scale (MADRS) (33) total score ≤16 at screening and baseline. In addition, the patients did not have any concurrent psychiatric disorder other than GAD or any prior history of psychiatric disorders such as manic or hypomanic episode, schizophrenia, or substance use disorder. Patients had no recent history of substance abuse or severe suicidal ideation or behavior and previously they responded to adequate treatment with SSRI or SNRI. The authors, Jie Fu and Lilei Peng, identified and agreed upon the studies meeting these criteria. The study quality was assessed with Jadad scores.12 The Jadad score is an instrument used to assess the quality of RCTs. It includes three items: randomization, blindness, and dropouts. The score standards and the results of our studies included are shown in Table 1. A total score ≥3 suggests that the study is of high quality. All of the studies included are of high quality.

Table 1 Jadad scores of the included studies

Data extraction

The information extracted included the study design, patient selection criteria, medical dose, trial duration, age, region of the study, baseline HAM-A rating scores, posttreatment HAM-A rating scores, the numbers randomized, and clinical outcomes. Clinical outcomes included response and adverse effects. The efficacy of vortioxetine was assessed in the intent-to-treat samples using the last observation carried forward in patients with at least one posttreatment rating. Response was defined as ≥50% decrease from baseline HAM-A total scores. Data were abstracted by one investigator and checked by a second investigator. Any discrepant data were again reviewed by the investigators to ensure that accurate data were obtained.

Statistical analysis

The number of responders, adverse effects, and individuals randomized into the vortioxetine and placebo groups for each trial were statistically combined using the Mantel–Haenszel random-effects or fixed-effects model. The effects were expressed as odds ratios (ORs) with 95% confidence interval (CI), test of significance (Wald Z), number of contrasts (N), and P-values. The overall OR for the meta-analysis was the mean of the ORs computed for each contrast weighted for sample size and the event rate. The incidence of adverse effects between the vortioxetine and placebo groups was determined using the Mantel–Haenszel model, and the results were expressed as the ORs with the 95% CI. A sensitivity analysis was performed to rule out the possibility that any single study strongly influenced the pooled effect. Publication bias was assessed with Egger’s test.13 Chi-square tests and the I2 statistic derived from the chi-square values were used to test heterogeneity among the contrasts. I2 values of 25%, 50%, and 75% indicated low, moderate, and high heterogeneity, respectively.14 The meta-analysis was conducted using RevMan 5.2 software (Cochrane Collaboration, London, UK) and Stata 10.0 software (StataCorp LP, College Station, TX, USA).

Results

After searching PubMed, Cochrane Library, PsycINFO, and the Clinical Trials databases; the abstracts of the annual meetings of the American Psychiatric Association; and previous reviews, four articles were included in the study (Table 2).15–18 The search flow diagram is shown in Figure 1. One recent article by Baldwin and Loft,19 published in July 2012, was excluded because that study focused on the efficacy and tolerability of vortioxetine in the prevention of relapse of GAD in patients with remission after acute treatment, which did not meet the inclusion criteria. Only information included in the publication was included in our meta-analysis.

Table 2 Overview of the included studies
Abbreviations: HAM-A, Hamilton Anxiety Scale; T, treatment group; C, control group.

Figure 1 Search flow for the trial identification and selection process.
Abbreviations: APA, American Psychiatric Association; RCT, randomized control trial.

Figure 2 Odds ratios (ORs) and 95% confidence intervals (CIs) of the individual studies and the pooled data for the included studies comparing the response rates between the groups treated with multiple doses of vortioxetine and placebo.
Notes: (A) 2.5 mg/d vortioxetine vs placebo, (B) 5 mg/d vortioxetine vs placebo, (C) 10 mg/d vortioxetine vs placebo, and (D) 2.5 mg/d vortioxetine vs 10 mg/d vortioxetine.
Abbreviations: M–H, Mantel–Haenszel; df, degrees of freedom.

Table 3 Main results of RCTs evaluating the efficacy of vortioxetine in GAD
Abbreviations: GAD, generalized anxiety disorder; RCT, randomized control trial; T, treatment group; C, control group.

Table 4 shows the common adverse effects related to vortioxetine in the treatment of GAD. The most common side effects were nausea and headache. Compared to placebo, nausea occurred more frequently following treatment with high doses (5 and 10 mg/d) of vortioxetine (OR=2.99, 95% CI=1.31–6.84, Z=2.60, P=0.009; OR=2.80, 95% CI=1.85–4.25, Z=4.85, P<0.00001, respectively) (Figure 3), but no significant differences were observed for headache (Figure 4). The sensitivity analysis indicated that the pooled response rate and adverse effects were not influenced when we tried to rule out any of the included studies (data not shown).

Table 4 Adverse effects in the vortioxetine and placebo groups
Note: “–” represents that side effect was not assessed.

Figure 3 Odds ratios (ORs) and 95% confidence intervals (CIs) of the individual studies and the pooled data for the included studies comparing the nausea rates between the groups treated with multiple doses of vortioxetine and placebo.
Notes: (A) 2.5 mg/d vortioxetine vs placebo, (B) 5 mg/d vortioxetine vs placebo, and (C) 10 mg/d vortioxetine vs placebo.
Abbreviations: M–H, Mantel–Haenszel; df, degrees of freedom.

Figure 4 Odds ratios (ORs) and 95% confidence intervals (CIs) of the individual studies and the pooled data for the included studies comparing the headache rates between the groups treated with multiple doses of vortioxetine and placebo.
Notes: (A) 2.5 mg/d vortioxetine vs placebo, (B) 5 mg/d vortioxetine vs placebo, and (C) 10 mg/d vortioxetine vs placebo.
Abbreviations: M–H, Mantel–Haenszel; df, degrees of freedom.

Due to a small number of trials in our meta-analysis, we used an Egger’s test (P=0.249) to determine if there was publication bias; the result indicated that no publication bias was found.

Discussion

This meta-analysis showed no significant improvement for vortioxetine in the treatment of GAD compared to placebo. Our results are not consistent with those of the previous meta-analysis.11 The previous meta-analysis conducted by Pae et al demonstrated statistically superior efficacy for vortioxetine in the treatment of GAD compared to placebo. The reason for the lack of congruence between these two meta-analyses may be the difference in the methodologies. The previous meta-analysis primarily relied on the analysis of a continuous measurement (HAM-A change from baseline) and all the randomized subjects were included in the analysis. However, our meta-analysis primarily relied on the categorical measure (% responders) and the analyses were separately performed according to the doses of vortioxetine. The sensitivity analysis of the previous meta-analysis showed that their results were unstable, whereas the overall outcomes of our meta-analysis were stable. In our meta-analysis, the pooled response rates were not influenced when we tried to rule out any of the included studies, which may be a large placebo response interfering with the ability to demonstrate vortioxetine’s benefits. The studies that showed negative results15–17 had a higher placebo response rate than those with positive results18,20 (data not shown). Furthermore, the negative results obtained might be due to the large sample size, which concealed the results of the studies with positive results, and the effect could not be overcome by the meta-analytic method.

In the clinical studies analyzed, the common adverse effects of vortioxetine included nausea and headache. However, these symptoms were mild to moderate in intensity.17,18 Our results indicated that nausea occurred more frequently following treatment with high doses (5 and 10 mg/d) of vortioxetine when compared to the placebo group. There were no significant differences for headache among different groups. A sensitivity analysis suggested that none of the included studies strongly determined the pooled adverse effects rate.

The response rate and the occurrence of nausea between the groups treated with 5 mg/d of vortioxetine and placebo had obvious heterogeneity. Many factors contributed to the significant heterogeneity. Of note, the negative studies had a strong placebo response, which likely contributed to the difficulty in detecting the effect of vortioxetine. Furthermore, other factors, including age (the mean age of one study18 was obviously found to be less than that of the other studies) and region, were different. Age may be an important factor which influences people’s response to the medicine. The two negative studies were conducted in the USA,16,17 while one positive study was conducted in both Europe and Africa.18 Difference in regions may influence the results due to their particular condition or implementation.

Sexual dysfunction often occurs when selective 5-HT reuptake inhibitors are administered for the treatment of mood disorders.21,22 This side effect adversely affects the quality of life of the patients with antianxiety and reduces the compliance with treatment. Recently, Bijlsma et al suggested that the sexual side effects of SSRI may be mediated by their inhibitory effects on dopamine signaling in the brain. Thus, the authors suggested that the clinical development of novel antidepressants or anxiolytics should focus on compounds that simultaneously increase both serotonin and dopamine signaling.23 In vivo nonclinical studies have demonstrated that vortioxetine enhances the levels of serotonin, noradrenaline, dopamine, acetylcholine, and histamine in specific areas of the brain.6 This may be the reason that vortioxetine does not significantly cause sexual dysfunction. In the studies included in our meta-analysis, only one study indicated that vortioxetine led to sexual dysfunction.16 Thus, we could not conclusively assess whether vortioxetine causes sexual dysfunction in the treatment of patients with anxiety. This potential side effect warrants additional research.

Limitations

The limitations of this meta-analysis are as follows: 1) A small number of studies are included and the sample size is relatively small, which may have influenced the reliability of the results. 2) Due to incomplete data, we did not compare the onset time between the groups treated with multiple doses of vortioxetine and placebo. 3) All of the included trials were supported by the Takeda Pharmaceutical Company Ltd as part of a joint clinical development program with H. Lundbeck A/S, which may have influenced the results. 4) Our meta-analysis only included the published clinical trials, so we may not have identified all RCTs investigating the effects of vortioxetine in patients with GAD, especially unpublished studies. The variation may influence the results and prevent us from conducting meta-analysis for other outcomes. 5) Due to incomplete data, we did not perform the efficacy analysis in the treatment of more severe anxiety (≥25 in baseline HAM-A total score) compared to placebo.

Conclusion

In conclusion, our meta-analysis of published RCTs showed that vortioxetine is not superior to placebo in reducing HAM-A scores in individuals with a primary diagnosis of GAD, and nausea was more frequent with higher doses. So the current evidences do not support using vortioxetine for the treatment of GAD. Due to the small number of trials in our meta-analysis, the results should be interpreted and translated into clinical practice with caution. In the future, more studies are needed to fully define the efficacy, optimal doses, and safety of vortioxetine in the treatment of GAD.

Disclosure

The authors report no conflicts of interest in this work.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5. Arlington, VA: American Psychiatric Publishing; 2013.

Goorden M, Muntingh A, van Marwijk H, et al. Cost utility analysis of a collaborative stepped care intervention for panic and generalized anxiety disorders in primary care. J Psychosom Res. 2014;77(1):57–63.

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Mahableshwarkar AR, Jacobsen PL, Chen Y, Simon JS. A randomised, double-blind, placebo-controlled, duloxetine-referenced study of the efficacy and tolerability of vortioxetine in the acute treatment of adults with generalised anxiety disorder. Int J Clin Pract. 2014;68(1):49–59.

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Trintellix vs Lexapro: Main Differences and Similarities

Trintellix (vortioxetine) and Lexapro (escitalopram) are two antidepressant medications that can treat depression or, more specifically, major depressive disorder (MDD). Lexapro can also treat anxiety disorders with less sexual side effects. As selective serotonin reuptake inhibitors (SSRI) type medications, Trintellix and Lexapro work to regulate serotonin in the brain. However, there are still some differences in how they are used.

Trintellix

Trintellix is also known by its chemical name, vortioxetine. Approved in 2013, Trintillex can treat MDD in adults. There is currently no generic version available yet.

Trintellix comes as a 5 mg, 10 mg, or 20 mg oral tablet. It can be taken once daily with or without food. Trintellix has a half-life of a few days and, unlike other SSRIs, can be discontinued abruptly.

Lexapro

Lexapro is the brand name for escitalopram. It was approved in 2002 to treat MDD in adults and adolescents aged 12 to 17 years old. Lexapro can also treat generalized anxiety disorder (GAD).

Lexapro is available in generic oral tablets with strengths of 5 mg, 10 mg, or 20 mg. It can be taken once daily with or without food and has a half-life of almost 2 days. Additionally, the dose must be reduced over time if the medication is being discontinued.

Trintellix vs Lexapro Side by Side Comparison

Trintellix and Lexapro are antidepressants that can treat similar conditions. Their main features and differences can be found below.

Trintellix Lexapro
Prescribed For
  • Major Depressive Disorder (MDD)
  • Major Depressive Disorder (MDD)
  • Generalized Anxiety Disorder (GAD)
Drug Classification
  • Selective Serotonin Reuptake Inhibitor (SSRI)
  • Selective Serotonin Reuptake Inhibitor (SSRI)
Manufacturer
  • Takeda Pharmaceuticals
  • Allergan
Common Side Effects
  • Nausea
  • Dizziness
  • Diarrhea
  • Insomnia
  • Abnormal dreams
  • Constipation
  • Vomiting
  • Dry mouth
  • Indigestion
  • Pruritus
  • Nausea
  • Dizziness
  • Diarrhea
  • Insomnia
  • Fatigue
  • Indigestion
  • Headache
  • Agitation
  • Shaking
  • Somnolence
  • Increased sweating
  • Decreased libido
  • Ejaculation Disorder
  • Anorgasmia
Is there a generic?
  • There is no generic currently available
  • Yes, Escitalopram
Is it covered by insurance?
  • Varies according to your provider
  • Varies according to your provider
Dosage Forms
  • Oral tablet
  • Oral tablet
  • Oral solution
Average Cash Price
  • $426 for a supply of 30, 10 mg tablets.
  • $379 for a supply of 30 tablets, 10 mg
SingleCare Discount Price
  • Trintellix Price
  • Lexapro Price
Drug Interactions
  • MAO inhibitors (isocarboxazid, phenelzine, selegiline, tranylcypromine)
  • CYP2D6 inhibitors (fluoxetine, paroxetine, etc.)
  • Other SSRIs
  • SNRIs
  • Triptans
  • Tricyclic antidepressants (amitriptyline, nortriptyline, imipramine)
  • Opioids
  • Lithium
  • Tramadol
  • Buspirone
  • St. John’s Wort
  • NSAIDs
  • Aspirin
  • Warfarin
  • Phenytoin
  • Carbamazepine
  • MAO inhibitors (isocarboxazid, phenelzine, selegiline, etc.)
  • Tricyclic antidepressants (amitriptyline, desipramine, doxepin, etc.)
  • Other SSRIs (citalopram, fluoxetine, sertraline, etc.)
  • SNRIs (duloxetine, venlafaxine, etc.)
  • Triptans (almotriptan, rizatriptan, sumatriptan, etc.)
  • Amphetamines (dextroamphetamine, levoamphetamine, lisdexamfetamine, etc.)
  • NSAIDs (celecoxib, etodolac, ibuprofen, aspirin etc.)
  • Warfarin
  • Pimozide
  • Buspirone
  • Cimetidine
  • Lamotrigine
  • Phenytoin
  • Carbamazepine
Can I use while planning pregnancy, pregnant, or breastfeeding?
  • Trintellix is in Pregnancy Category C. Adequate studies have not been performed in humans. Consult a doctor regarding steps to take while pregnant and breastfeeding
  • Lexapro is Pregnancy Category C. Animal studies have shown adverse effects to the fetus. Adequate studies have not been performed in humans. Lexapro is not expected to harm breastfed infants. Consult a doctor regarding steps to take while pregnant and breastfeeding

Summary

Trintellix (vortioxetine) and Lexapro (escitalopram) are brand-name SSRI type medications that can treat depression as MDD. Both medications are taken once daily depending on a doctor’s instructions. Lexapro can also treat anxiety.

Trintellix and Lexapro can be taken with or without food. While they have similar side effects such as nausea and dizziness, these side effects usually go away after consistent use. Trintellix is known to cause less sexual side effects than other SSRIs. Therefore, it is a better alternative for those who suffer from libido problems with other antidepressants.

Deerfield, IL, October 22, 2018– Takeda Pharmaceuticals U.S.A., Inc. (“Takeda”) and Lundbeck today announced that the U.S. Food and Drug Administration (FDA) approved a supplemental new drug application (sNDA) for TRINTELLIX® (vortioxetine), a prescription medication used for adults with major depressive disorder (MDD), also known as depression.

The TRINTELLIX U.S. prescribing information now includes head-to-head clinical study data that demonstrated superiority to a commonly-used selective serotonin reuptake inhibitor (SSRI), Lexapro® (escitalopram) in improving treatment-emergent sexual dysfunction (TESD). In the study, patients with well-treated depression who were experiencing TESD while taking an SSRI (paroxetine, sertraline or citalopram) were switched to TRINTELLIX or escitalopram. This is the first time an antidepressant has included data of this type in its labeling. These data build upon the voluntary and prospective reports of sexual dysfunction with TRINTELLIX in clinical trials.

“Sexual dysfunction is one of the most common and bothersome side effects patients with depression struggle with when prescribed an SSRI,” said lead study investigator, Dr. Anita Clayton, Chair, Department of Psychiatry & Neurobehavioral Sciences, University of Virginia School of Medicine. “We designed the study to specifically look at these troublesome side effects. Changing to a medication with potentially fewer sexual side effects, while not losing progress in treating depression, provides an important option for patients with depression.”

TESD can affect any aspect of the sexual response cycle including desire, arousal and orgasm.

In an eight-week head-to-head, randomized, double-blind study, well-treated adult MDD patients with TESD (N=447) were switched to TRINTELLIX (N=225) or escitalopram (N=222), from citalopram, paroxetine, or sertraline, due to SSRI-induced sexual dysfunction. For both TRINTELLIX and escitalopram, patients were started on 10 mg, increased to 20 mg at week one, followed by flexible dosing (10 mg or 20 mg). TRINTELLIX demonstrated statistically significant improvement vs. escitalopram from baseline to week eight as measured by mean Change in Sexual Functioning Questionnaire Short Form (CSFQ-14) Total Score (8.8 vs. 6.6, p=0.013). Both drugs maintained prior improvement in depression based on overall score on standardized depression rating scale.

“There remains a need for effective antidepressants that may have less impact on sexual function. We are pleased with the FDA’s decision to approve the addition of this meaningful comparative data in the U.S. labeling of TRINTELLIX,” said Dr. Louis Mini, Medical Head, Neuroscience, U.S. Medical Office, Takeda.

“One of our key priorities is to develop treatment options for depression that address what matters to patients. We aim to find ways patients can get the most benefit from therapy and this news is a step forward with that goal,” said Doug Williamson, Chief Medical Officer and Vice President, U.S. Medical, Lundbeck.

In the five years since FDA approval on September 30, 2013, more than 845,000 patients have been prescribed TRINTELLIX. Vortioxetine is approved in 77 countries and available in more than 60 countries to date. This is the second time this year FDA has approved an sNDA for TRINTELLIX to add new data to the TRINTELLIX U.S. labeling.

About Major Depressive Disorder (MDD)

MDD is a complex mental health illness that affects approximately 16 million people annually. Also known as clinical depression, MDD is the leading cause of disability worldwide and a major contributor to the overall global burden of disease.MDD may trigger emotional, cognitive and physical symptoms, which includes depressed mood, loss of interest or pleasure, significant weight loss or gain or change in appetite, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue or loss of energy, feelings of worthlessness or excessive guilt, diminished ability to think or concentrate, or indecisiveness, and recurrent suicidal ideation.

About TRINTELLIX (vortioxetine)

The mechanism of the antidepressant effect of TRINTELLIX is not fully understood. It is an inhibitor of serotonin (5-HT) reuptake and that is thought to be a mechanism of its action. It is also an agonist at 5-HT1A receptors, a partial agonist at 5-HT1B receptors and an antagonist at 5-HT3, 5-HT1D and 5-HT7 receptors. The contribution of each of these activities to TRINTELLIX’s antidepressant effect has not been established. It is considered to be the first and only compound with this combination of pharmacodynamic activity. The clinical relevance of this is unknown.

The most commonly observed adverse events in MDD patients treated with TRINTELLIX in 6-8 week placebo-controlled studies (incidence greater than or equal to 5 percent and at least twice the rate of placebo) were nausea, constipation and vomiting. Overall, 5 to 8 percent of the patients who received TRINTELLIX 5 to 20 mg/day in short-term trials discontinued treatment due to an adverse reaction, the most common being nausea, compared with 4 percent of placebo-treated patients in these studies. TRINTELLIX and other antidepressants may cause serious side effects. See Important Safety Information below.

Voluntary reports of sexual dysfunction with TRINTELLIX in 6-8 week controlled trials were <5%. Because voluntary reports of sexual dysfunction are known to be underreported, a separate, self-rated questionnaire was provided to patients prospectively in TRINTELLIX clinical studies. When assessed proactively in patients without sexual dysfunction at baseline, reports of treatment emergent sexual dysfunction across doses 5 mg, 10mg, 20 mg were 16%, 20%, 29% in males (N=212) respectively and females 22%, 23% and 34% (N=226) respectively, compared to 14% (N=162) and 20% (N=135), respectively, in placebo.

In clinical studies, TRINTELLIX had no significant effect on body weight as measured by the mean change from baseline in 6-8 week placebo-controlled studies. In the 6-month, double-blind, placebo-controlled phase of a long-term study in patients who had responded to TRINTELLIX during the initial 12-week, open-label phase, there was no significant effect on body weight between TRINTELLIX and placebo-treated patients. Some reports of weight gain have been received since product approval. TRINTELLIX has not been associated with any clinically significant effects on vital signs, including systolic and diastolic blood pressure and heart rate, as measured in placebo-controlled studies.

TRINTELLIX was discovered by Lundbeck researchers in Copenhagen, Denmark. The clinical trial program in the U.S. was conducted jointly by Lundbeck and Takeda, and Takeda holds the new drug application for the U.S. market. TRINTELLIX is a trademark of H. Lundbeck A/S and is used under license by Takeda Pharmaceuticals U.S.A., Inc. For more information, visit www.Trintellix.com.

The World Health Organization has issued an Anatomical Therapeutic Chemical (ATC) code for TRINTELLIX that places it in the category of “Other” antidepressants.

The recommended starting dose of TRINTELLIX is 10 mg once daily without regard to meals. The dose should then be increased to 20 mg/day, as tolerated, because higher doses demonstrated better treatment effects in trials conducted in the U.S. A dose decrease down to 5 mg/day may be considered for patients who do not tolerate higher doses. The available doses provide important flexibility for physicians to help address the variability of patient needs.

TRINTELLIX is available as 5 mg, 10 mg and 20 mg tablets.

IMPORTANT SAFETY INFORMATION

Suicidal Thoughts and Actions and Antidepressant Drugs

Antidepressants may increase suicidal thoughts or actions in some children, teens or young adults within the first few months of treatment or when the dose is changed. Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. People who have (or have a family history of) bipolar illness, or suicidal thoughts or actions may have a particularly high risk. Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts or feelings. Call your healthcare provider right away if symptoms such as anxiety, irritability, impulsivity, trouble sleeping, aggressive behavior or suicidal thoughts are new, worse or worry you. TRINTELLIX has not been evaluated for use in patients under 18.

Do not take TRINTELLIX if you:

  • Are allergic to vortioxetine or any of the ingredients in TRINTELLIX
  • Take a Monoamine Oxidase Inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid; do not take an MAOI within 21 days of stopping TRINTELLIX; do not start TRINTELLIX if you stopped taking an MAOI in the last 14 days

TRINTELLIX may cause serious side effects including:

Serotonin Syndrome: A potentially life-threatening problem that can happen when medicines such as TRINTELLIX are taken with certain other medicines. Symptoms may include agitation, hallucinations, coma or other changes in mental status; problems controlling movements or muscle twitching, stiffness or tightness; fast heartbeat, high or low blood pressure; sweating or fever; nausea, vomiting or diarrhea.

Abnormal bleeding or bruising: TRINTELLIX and other serotonergic antidepressant medicines may increase your risk of bleeding or bruising, especially if you take the blood thinner warfarin (Coumadin®, Jantoven®), a non-steroidal anti-inflammatory drug (NSAID), or aspirin.

Manic episode: Symptoms may include greatly increased energy; severe trouble sleeping; racing thoughts; reckless behavior; unusually grand ideas; excessive happiness or irritability; talking more or faster than usual.

Visual problems: May include eye pain, changes in vision, swelling or redness in or around the eye. Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are.

Low salt (sodium) levels in the blood: Symptoms may include headache; difficulty concentrating, memory changes or confusion; weakness and unsteadiness on your feet; and in severe or sudden cases hallucinations, fainting, seizures or coma. If not treated, severe low sodium levels can cause death.

Before starting TRINTELLIX, tell your healthcare provider if you have or had liver problems, seizures or convulsions, bipolar disorder (manic depression) or mania, low salt (sodium) levels in your blood, bleeding problems, drink alcohol, have any other medical conditions or if you are pregnant, nursing, plan to become pregnant, or plan to nurse.

TRINTELLIX and some medicines may interact with each other, may not work as well, or may cause serious side effects when taken together. Tell your healthcare provider if you plan on or are taking any other prescription and non-prescription medicines, vitamins and herbal supplements including medicines for migraine headaches, such as triptans; medicines used to treat mood, anxiety, psychotic or thought disorders such as tricyclics, lithium, SSRIs, SNRIs, bupropion, buspirone or antipsychotics; MAOIs including linezolid (a specific antibiotic); over-the-counter supplements such as tryptophan or St. John’s wort; and the following medicines: aspirin, NSAIDs, warfarin (Coumadin®, Jantoven®), diuretics, rifampin, carbamazepine, phenytoin, quinidine, tramadol or fentanyl.

Common side effects of TRINTELLIX include: nausea, constipation or vomiting. These are not all the possible side effects of TRINTELLIX.

Do not start or stop taking TRINTELLIX without talking to your healthcare provider first. Suddenly stopping TRINTELLIX when you take higher doses may cause you to have side effects including headache, stiff muscles, mood swings, sudden outbursts of anger, dizziness or feeling lightheaded, or runny nose.

Talk to your healthcare provider.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit https://www.fda.gov/medwatch or call 1-800-FDA-1088.

Indication for TRINTELLIX

TRINTELLIX is a prescription medicine used to treat Major Depressive Disorder (MDD) in adults.

Please see accompanying Prescribing Information, including Medication Guide for TRINTELLIX.

About Takeda Pharmaceutical Company Limited

Takeda Pharmaceutical Company Limited (TSE: 4502) is a global, research and development-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its R&D efforts on oncology, gastroenterology and neuroscience therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. Innovative products, especially in oncology and gastroenterology, as well as Takeda’s presence in emerging markets, are currently fueling the growth of Takeda. Around 30,000 Takeda employees are committed to improving quality of life for patients, working with Takeda’s partners in health care in more than 70 countries. For more information, visit https://www.takeda.com/newsroom/.

Takeda Pharmaceuticals U.S.A., Inc. is located in Deerfield, Ill., and is the U.S. marketing and sales organization of Takeda Pharmaceutical Company Limited.

Additional information about Takeda is available through its corporate website, www.takeda.com, and additional information about Takeda Pharmaceuticals U.S.A., Inc. is available through its website, www.takeda.us.

About Takeda Neuroscience

Neuroscience is a core therapeutic area for Takeda. Our mission is to bring innovative medicines to patients suffering from neurologic and psychiatric diseases for whom there are no treatments available. We identify targets either genetically linked with specific neurologic or psychiatric disorders or with high association to the disease pathophysiology, design and operationalize clinical trials in novel ways in an effort to overcome historical challenges, and collaborate with patients, academic institutions, pharmaceutical and biotechnology partners, payors, regulators and prescribers to integrate their unique expertise and perspective. The current Takeda Neuroscience global portfolio consists of five approved medicines, which treat adults with Major Depressive Disorder, Alzheimer’s-type dementia, insomnia, multiple sclerosis, and Parkinson’s disease.In addition, there are many assets in clinical development for targeted patient populations.

About H. Lundbeck A/S

H. Lundbeck A/S (LUN.CO, LUN DC, HLUYY) is a global pharmaceutical company specialized in psychiatric and neurological disorders. For more than 70 years, we have been at the forefront of research within neuroscience. Our key areas of focus are Alzheimer’s disease, depression, Parkinson’s disease and schizophrenia.

Our approximately 5,000 employees in 55 countries are engaged in the entire value chain throughout research, development, manufacturing, marketing and sales. Our pipeline consists of several late-stage development programs and our products are available in more than 100 countries. We have production facilities in Denmark, France and Italy. Lundbeck generated revenue of DKK 17.2 billion in 2017 (EUR 2.3 billion; USD 2.6 billion).

For additional information, visit www.lundbeck.com and connect on Twitter at @Lundbeck.

Lundbeck in the U.S.

In the U.S., Lundbeck employs more than 800 people focused solely on accelerating therapies for brain disorders. With a special commitment to the lives of patients, families and caregivers, Lundbeck U.S. actively engages in hundreds of initiatives each year that support our patient communities.

For additional information, visit www.lundbeckus.com and connect on Twitter at @LundbeckUS.

Takeda Pharmaceutical Company Limited Contact

U.S. media
Alicia Highlander
Tel: +1-224-554-1426
Email: [email protected]

Lundbeck Contact

U.S. media
Ashleigh Duchene
Tel: +1-312-802-2906
Email: [email protected]

How can I lose weight while on antidepressants?

I am exercising and eating well and still can’t seem to shed the pounds. I am on antidepressants. What can I do?

Losing weight is often a struggle, especially when a person is also living with a mood disorder. The causes are multiple. Increased appetite and carbohydrate craving, along with reduced activity level, are common symptoms of depression. And yes, certain antidepressants and other medications may increase appetite. However, most medications do not alter metabolism, per se. Thus, weight loss can still occur when attention is given to other factors, including the composition and timing of dietary intake.

Eating more frequently and smaller amounts, increasing the relative amount of protein eaten (people generally feel more “full” when eating high protein content foods), reducing breads and starches, eating a healthful breakfast, and avoiding large meals or snacks late in the evening can provide a more balanced diet throughout the entire day.

If one believes their current efforts to lose weight should be more productive, a consultation with a nutritionist may be helpful. If that isn’t possible, keeping a written log of one’s consumption may provide clues to problem areas and reinforce better dietary habits. In particular, check out the nutritional content of commonly eaten foods and foods believed to be “healthy”.

Several readily available websites and phone apps list nutritional information for prepared and restaurant food items, and provide logs for recording consumption. We are often unaware of the hidden calories in many foods we eat. Even so-called “low fat” or “no fat” foods may be loaded with empty carbohydrates. Soft drinks, sport drinks, energy bars, restaurant salads and salad dressings may contain excessive amounts of sugar. Alcoholic beverages such as wine and beer are also loaded with carbohydrates and are a source of excessive calorie intake for some individuals.

Another critical ingredient for weight loss is exercise. Increasing both aerobic exercise and strength training, ideally four times a week for a minimum of 30 to 45 minutes, can increase muscle tone and metabolism and reduce fat stores. Regular exercise has also been shown to reduce risk for depression relapse when combined with a stable medication regimen. If one is already exercising regularly, changing up your routine and challenging your body in novel ways with repeated bursts of exertion can make your work-outs more efficient.

Chronic, low-grade sleep deprivation is another contributor to obesity. Skipping sleep leads to persistently elevated levels of the body’s stress hormone, which can cause elevated blood sugar levels and increased fat stores. Staying up late may also make one more prone to late night snacking.

Lastly, a person carefully tending to all the above yet still gaining weight should consult their physician. Certain medical conditions such as thyroid abnormalities can cause weight gain as well as complicate depression.

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