Risperidone for depression and anxiety


How long does risperidone stay in your system?

I tell you what, there’s no way in hell that the crap in risperdal / risperidone left my body in 5 days! It took about 8 months of hardcore cardio exercise for me to purge this poison from my system. I would sweat so much after I tapered off of this, and it would smell like putrid chemicals, and definitely not something that would ever come from a human being..
Please NEVER take this stuff unless you want to be chemically lobotomized..
It’s so funny to read all kinds of “educated comments” from people who’ve never taken this poison.. ie, doctors.. Like they’re “experts” or something.. Most of our doctors are getting their education about these drugs from pharma companies or professors that have been bought and paid for by big pharma.. I’d like medical knuckleheads to try benzos and/ or risperdal for several months / years daily, and then tell me how they feel, and that there’s no “discontinuation issues” when they try to get off of these terribly dangerous drugs..
What’s happening with these drugs that are supposed to “help people” is criminal, but doctors and big pharma aren’t being held accountable. They should be tried for “crimes against humanity”, and severely sentenced.
Risperdal slowly took away my soul and all of the things that made it fun to be me. I’m 6 months off of it, after being on it for 4.5 years. It was positioned to me as a very safe, “mood stabilizer”, yeah right.. It made me stupid and made me gain weight, I’m glad I didn’t get the man boobs, or TD..
A couple of months off of it, my hard exercise began to pay off, and I’ve dropped 30 lbs.. my face looks less swollen and my body isn’t bloated anymore.. It was very difficult to taper off of, but now I have a chance to live. I firmly believe this stuff will ruin your life, and then kill you if you stay on it..


Side effects

Some side effects that appear should disappear or get better after a few days. If they do not, you should go back to your doctor.

Don’t stop taking risperidone until you talk to your doctor or you may get withdrawal symptoms as well.

Very common side effects of taking risperidone (affecting more than one in ten people) include:

  • headache – speak to your pharmacist about treatments to help
  • dizziness or low blood pressure – try not to stand up too quickly or sit or lie down if you’re feeling dizzy
  • movement problems, sometimes called extra-pyramidal side effects (EPSEs). This is a medical term that includes many symptoms relating to movement. Symptoms include: muscle stiffness or tightness; jerks when bending your arms and legs; your movements might feel a bit robotic; shakiness in your hands and legs; and feeling restless all the time and needing to move around. If you develop EPSEs, your doctor may decrease your dose or give you other treatments to help

Common side effects of taking risperidone (affecting up to one in ten people) include:

  • feeling sleepy, tired, weak or exhausted – this can be worse at the start of treatment and wear off after a few weeks. If you take your dose once daily, you could try taking it just before you go to bed
  • nausea (feeling sick) or vomiting (being sick) – try taking your dose with food
  • diarrhoea (loose poo) – make sure you drink lots of water and speak to your doctor or pharmacist if it continues for more than a few days
  • constipation (finding it hard to poo) – make sure you drink enough fluids, eat enough fibre (like brown breads, fruit and veg) and do enough exercise. Speak to your pharmacist if this goes on for a few more days than is normal for you
  • increased appetite, decreased appetite or eating less, weight gain or weight loss – try to eat lots of veg and fibre when you can. Speak to your pharmacist or doctor for advice on healthy foods
  • heartburn, abdominal (gut) pain or discomfort
  • higher level of a hormone called prolactin. This can cause periods to stop, or milk to leak from your breasts. It can also cause trouble getting an erection. Speak to you doctor if you get any of these symptoms and they can check your prolactin level with a simple blood test. In the long term, raised prolactin can weaken your bones

Although this list of side effects can look scary, some people won’t get any side effects at all. Speak to your pharmacist or doctor if you think you are having side effects from risperidone.
There are other side effects that you can get when taking this medicine – we have only included the most common ones here. Please look at the leaflet inside your medicine box, or ask a doctor or pharmacist, if you want to know whether you are getting a side effect from your medicine.

If you do get a side effect, please think about reporting it via the Yellow Card Scheme.

Do not stop taking the tablets until you talk to your doctor, or you may get withdrawal symptoms as well.

Young people and children aged 5-17 are more likely than adults to get the following side effects:

  • feeling tired, sleepy, or less focused
  • headache
  • increased appetite
  • vomiting (being sick)
  • getting cold symptoms like a blocked nose and cough
  • abdominal (gut) pain
  • fever
  • dizziness and shaking
  • diarrhoea (loose poo) and incontinence (less control over when you wee)


Risperidone use has been linked to high blood sugar and diabetes in some young people. This could be linked to putting on weight.

Watch out for any early signs of diabetes: wanting to drink a lot, going for a wee a lot, feeling hungrier and feeling weak.

If you already have diabetes, taking risperidone may affect your blood sugar levels. Talk to your doctor and check your blood glucose levels regularly if this applies to you. You may have to increase the medication you use for your diabetes.

A side effect of risperidone may be either weight loss or weight gain.

Weight gain is more common than weight loss.

It is very difficult to know how it will affect each person who takes it. If you start to have problems with your weight while taking risperidone, talk to your doctor or pharmacist about this.

Your doctor should measure your weight regularly when you are taking risperidone.

Most of the weight gain is in the first six to 12 months, and then it levels out.

As you grow you will gain weight naturally, but anything more than that should be watched.

Good practice for doctors suggests this routine for checking the weight of people who start taking antipsychotic medicines like risperidone:

  • get your weight noted before you start
  • get your weight checked every week for the first six weeks and then again after three months
  • get your weight and waist measurement checked at least every six months

You could take these measurements yourself and keep a chart to show your doctor.

If you put on weight, there are other antipsychotic medicines you can try which are less likely to make you put on weight.

Look at ways to try and lose extra unwanted weight.


You can feel sleepy in the first few days of taking risperidone. This should get better after the first week or two.

If you feel like a zombie, and you’ve been taking it for more than a month, you should go back to the doctor and see what else you can do.

Risperidone can make some people find it hard to get to sleep. If this happens, you can change the time that you take your risperidone each day (if you are taking tablets or liquid). Take it earlier in the day and see if this makes it easier to get to sleep.

If you are on the long-acting injection, talk to your doctor if your sleep is disturbed.

Sex and fertility


Risperidone can have side effects that affect your sex life, including:

  • painful erections, or problems getting an erection (getting hard) and ejaculating (coming)
  • periods may become irregular or stop due to raised prolactin levels. Talk to your doctor and they will be able to do a simple blood test to check if the risperidone is the cause
  • some bleeding from the vagina, and difficulty reaching orgasm the same way as before
  • some breast growth and milk flow, regardless of gender
  • decrease in libido (sex drive)

These effects should pass after the first couple of weeks. If they do not, and this is a problem for you, go back to the doctor and see what else you could try.


While taking risperidone it might be more difficult for you to fall pregnant, but this effect is not permanent.

Risperidone can increase the level of a natural hormone called prolactin in the body.

This hormone is produced in high levels to produce milk in breastfeeding mothers and provides some natural contraception.

Prolactin is produced at low levels in men.

This means it may be more difficult to get pregnant if your prolactin levels rise. Do NOT rely on this as an alternative to good contraception.

Talk to your doctor about this if you want to get pregnant, and see below for more information about taking risperidone during pregnancy

Pregnancy, post-natal and breastfeeding


When deciding whether to take risperidone during pregnancy it is important to weigh up how necessary risperidone is to your health against the possible risks to you or your baby, some of which will depend on how many weeks pregnant you are.

Remaining well is particularly important during pregnancy and while caring for a baby. Treatment with risperidone in pregnancy may be the best option for both mother and baby.

As with other antipsychotics, taking risperidone may cause your folate levels to become low and a prescribed supplement dose of 5mg daily should be taken.

There is information on over 400 mums who took risperidone and there does not seem to be an increased risk of malformations, miscarriage or diabetes during pregnancy.


If you have taken risperidone close to delivery your baby may have some side effects or such as being irritable, crying or problems feeding, and sleeping are usually mild and go away in a few days without treatment.


Risperidone is passed to the baby through breast milk in small amounts. This could help with any discontinuation symptoms.

You should discuss the risks and benefits of breastfeeding with your midwife or doctor.

Remember that it is important for you to remain well while you are bonding with and looking after your baby. For this reason, it may be best to take medicine for your mental health when breastfeeding.

Make sure that your doctor, nurse, or health visitor checks your baby for any side effects.

If your baby was premature or has health problems, then you will need to be extra careful about taking medicines while breastfeeding. It may be best not to breastfeed if this is the case, but you should discuss this with your doctor or midwife.

Driving and transport

Taking risperidone may make you feel tired or dizzy, and may affect your eyesight when you start taking it.

This could affect you if you drive a car, ride a bike, or do anything else that needs a lot of focus. It might be best to stop doing these things for the first few days, until you know how it affects you.

Don’t worry – most people drive as normal while taking risperidone.

You must tell The DVLA (Driver and Vehicle Licensing Agency) if you have bipolar disorder, schizophrenia, schizoaffective disorder or other mental health conditions that could affect your driving.

You can be fined up to £1,000 if you do not tell The DVLA about a medical condition that affects your driving.

You may be prosecuted if you are involved in an accident as a result.

School and exams

Try not to take risperidone for the first time just before your exams.

Taking risperidone may make you feel tired or make it hard to fall asleep at night. It can also give you headaches or affect your eyesight.

You should talk to your doctor about any future exams if you are starting risperidone.

You might decide together to delay starting it until you have done them.

If they are more than a month away, however, you might find that it is better to start risperidone to improve your motivation to study.

Don’t worry – most people take exams as normal while taking risperidone.

Psychosis and schizophrenia themselves can also affect concentration.

Friends and family

You may want to let your family and friends know you are taking risperidone so they can support you and help you look out for side effects.

For guidance on this, check out our page on getting support with your medication.


Risperidone is not a banned substance in sport.

Taking risperidone may make you feel tired and dizzy, and affect your eyesight

This could be dangerous in some sports like cycling or driving.

It might be best to stop such sports for the first few days, until you know how it affects you.

Don’t worry – most people play sports as normal while taking risperidone.

Alcohol and street drugs


You can continue to drink alcohol in moderation while taking risperidone. You might find having the two together makes you very sleepy, so during the first few days it might be best to stop drinking alcohol until you see how the medicine affects you.

If you want to drink alcohol, remember that you might be sleepy and make sure you can get home safely.

Street drugs

Some street drugs can increase levels of dopamine in the brain (e.g. cocaine, cannabis, ecstasy). As antipsychotics block the effects of dopamine, the ‘high’ from street drugs may not be as ‘high’ as before. You may therefore be tempted to increase the dose of your street drug to make up for it, but this could be dangerous.

Cannabis and other drugs may have their own side effects on your mental health, like anxiety or psychosis. For more information, have a look at our drugs and alcohol page.

Some street drugs can make you feel sleepy and this could be made worse with risperidone.

There are many other street drugs, but we don’t know what effect taking them with risperidone will have.

Risperidone can produce a false positive test for LSD on a urine drug screen.

Talk to your doctor about this if it is a problem for you.

Prescription medicines

Risperidone can interact with some other medicines and drugs

Check with your doctor or pharmacist whether risperidone is OK for you to take if you are on any other medicines.

If you have any further questions about this, you should speak to your doctor or pharmacist.

Always talk to the doctor if you are taking other medicines. Tell the pharmacist you are taking risperidone if you buy medicines (including things you put on your skin) for common illnesses.

References and further reading

For more helpful links and information, have a look at our references and further reading page.

How Long Does it Take to Get Invega Out of Your System?

Invega (Paliperidone) is a highly popular antipsychotic that has been repeatedly associated with serious side effects, gynecomastia being one of the most prevalent.

Gynecomastia, or male breast growth, occurs due to an extreme hormonal imbalance allegedly caused by Invega. This concern has led many patients to ask ‘how long does it take for Invega to get processed through the body?’

Patients taking Invega should ask their doctors for more accurate estimations, as it varies between patients. However, according to drugs.com, Invega has a long half life range that can last between 25 to 49 days.

It is important to note that it can take between five to six half lives for the body to completely process the drug, so patients can expect it to take between 150 to 300 days for their last Invega dose to leave their system.

Once again, patients should immediately consult their physicians to ask these questions as the numbers listed above are the estimations provided from Invega prescription information retrieved from drugs.com.

Different factors that effect the drug’s duration and impact include age, health, weight, metabolism, and other individual factors, so an exact approximation is difficult. Patients can expect a long withdrawal period, however, and should be monitored by a medical professional.

Patients who are concerned over the Invega gynecomastia controversy, or believe they may be developing man boobs, should also talk to their physicians about switching to a new medication.

Early intervention is needed to stop male breasts from further development; early intervention will hopefully prevent the need for more extreme treatments like surgical breast removal.

Overview of Invega Gynecomastia

Gynecomastia can be a psychologically devastating condition for young boys, as it primarily occurs in young male Invega patients around adolescence.

Due to the hormone fluctuations in the body during this vital developmental period, young boys are especially vulnerable to the hormonal side effects Invega presents.

Invega is an antipsychotic medication that is normally prescribed to adults and children with extreme psychological disorders. It works by leveling dopamine and serotonin levels. However, in doing this, Invega naturally causes the body to increase its prolactin levels.

Prolactin is the hormone primarily responsible for breast growth in young girls, and is produced in very small amounts in young boys.

But Invega causes the prolactin levels to be produced at much higher levels, leading to significant breast growth in men. Some patients have reported man boobs as large as 38D, as well as nipple pain and discharge.

Young boys who suffer gynecomastia often have to undergo liposuction and other forms of surgery to remove the excess breast tissue, and have to contend with chronic psychological trauma.

Even though this is a very serious condition, manufacturer Janssen Pharmaceuticals allegedly failed to warn patients against this side effect.

Young boys who have developed gynecomastia soon after taking Invega may be able to file legal action. Potential claimants should contact a specialized lawyer, to determine if they are eligible for an Invega gynecomastia lawsuit.

What Parents Should Know About Risperdal

Risperdal is a medication that’s widely used to treat children who are aggressive or excessively irritable. Though it was originally approved to treat psychosis, its use in children, including those with autism or ADHD diagnoses, has grown dramatically over the last two decades. That’s because Risperdal can successfully calm down kids with severe behavior problems, enabling them to function in school and within their families. Without it, some would require residential treatment.

But Risperdal (generic name risperdone) can have serious side effects, and it’s important to make sure a child taking it is monitored carefully. Parents should know what the medical community agrees are the “best practices” to be followed by a doctor who prescribes Risperdal, to insure good treatment.
Here are the basics about Risperdal: what it’s used for, potential side effects, and how a child on Risperdal should be monitored.

What is Risperdal for?

Risperdal is what is called an atypical, or second-generation antipsychotic (SGA). It was a new kind of antipsychotic approved by the Federal Drug Administration in the 1990s to treat the symptoms of psychosis in schizophrenia and bipolar disorder.

Now it is more widely used to treat aggression and irritability in both dementia patients, often in inpatient facilities, and in children.

Many kids on the autism spectrum take Risperdal to reduce behavior problems like aggression or self-injury, and the FDA has approved it for that use. But it’s also prescribed to many kids who have ADHD (attention-deficit hyperactivity disorder), ODD (oppositional defiant disorder) or DMDD (disruptive mood dysregulation disorder).

When kids act out dangerously or are at risk of getting kicked out of school or removed from the home, they may be given Risperdal or another SGA to calm them down. For kids who do not have an autism diagnosis, these prescriptions are off-label — that is, they are not an FDA-approved use for the drug. But a substantial body of evidence suggests they are effective in reducing persistent behavioral problems.

Why is Risperdal controversial?

Risperdal is controversial because side effects that include substantial weight gain and metabolic, neurological and hormonal changes that can be harmful. Some experts are concerned that children are being treated with the drug in lieu of other treatment — including behavioral treatment — that could be effective without the risk of these side effects.

Risperdal has been in the news over the last several years because of thousands of lawsuits from families who say they were not informed about side effects that might adversely affect their kids, and the kids were not taken off the medication when problems developed. Many of the suits are on behalf of boys who, in a rare side effect, developed breasts because of an increase in a hormone called prolactin.

Problems in school and at home

Wendy Nash, MD, a child and adolescent psychiatrist at the Child Mind Institute, describes a common scenario in which Risperdal is prescribed because a child’s aggressiveness or irritability has become acutely problematic. This behavior often presents in early adolescence, says Dr. Nash. “These are kids who are very aggressive, meaning they might push, shove, punch, break furniture.”

When these kids can’t control their tempers, they may be a danger to other children, their parents and themselves. “Sometimes their parents are so desperate they have considered calling 911,” Dr. Nash notes. Or the child might already have been sent to the emergency room after an outburst at school.

For kids in crisis, Risperdal is often clinicians’ first choice for stabilizing the situation. If it’s not a crisis, they recommend that other treatments be tried first.

Behavioral therapy

Most experts, including Dr. Nash, stress the importance of thoroughly investigating the causes of aggressive behavior as part of the evaluation for medication. Behavior problems can have many different sources, including undiagnosed anxiety, ADHD, learning disorders, trauma and medical problems. Treating those problems may allieviate the behavior issues in a more effective (and lasting) way than giving the child antipsychotic medication.

For children with disruptive behavior problems that haven’t reached a crisis stage, experts’ first choice for treatment is behavioral therapy, including parent training, to rein things in. Depending on the level of risk, Dr. Nash says she might recommend a first trial of behavioral therapy, or medication together with behavioral therapy.

Related: Choosing a Parent Training Program

Alternative medications

In a more stable situation, Dr. Nash also favors first trying more targeted medications with fewer side effects. For instance, in a child with ADHD, stimulants (Ritalin or Aderall) or non-stimulant ADHD medications like clonidine (Catapres, Kapvay, Nexiclon) or guanfacine (Estulic, Tenex, Intuniv) could reduce impulsive aggression. For a child with ODD, she says, antidepressants (SSRIs) can help with underlying depression or anxiety that could trigger outbursts.

If these attempts are not effective, Dr. Nash may try an SGA. Abilify (aripiprazole), which is also approved for irritability in kids on the spectrum and commonly used for aggression, is usually her first choice, because it has fewer side effects, than Risperdal, including lower weight gain and endocrine disruption. But medication treatment should always be in combination with behavioral therapy, she stresses, which could include parent training.

The medical community agrees. A survey of treatment recommendations from top experts emphasizes that medication should not replace behavioral therapy.

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After kids are stabilized

Experts note that a child who’s been put on an SGA in a crisis might be transitioned to a different treatment after the situation is stabilized. In Dr. Nash’s experience, children who participate in behavioral therapy may later be able to stop taking the medication. “My preference is to use risperidone in a time-limited way, to settle the crisis,” she explains. “In the meantime, I’m setting up parent management training.”

Michael Milham, MD, PhD, a child and adolescent psychiatrist at the Child Mind Institute, also uses SGAs to stabilize children in crisis situations. He notes that it’s critical to not take kids off the medications without other supports in place, such as behavioral therapy, including parent training.

“It’s important to know when to try to take kids off it — and it’s not as soon as things are going well,” explains Dr. Milham. “They need to be stable, and have other interventions in place. Otherwise you’re just going to recreate the problem, and the kids end up in the ER.”

Risperdal side effects

Weight gain

The most common side effect of Risperdal is weight gain, which can occur quickly. In one study, average weight gain after 10.8 weeks of treatment with Risperdal was 11.7 pounds, compared to just .44 pounds in children taking a placebo. In a study of children treated with Risperdal for 2.9 years, a third were either overweight or obese. Larger doses were associated with significantly greater increases in weight.

Metabolic side effects

Risperdal may also cause what are called “metabolic abnormalities,” including a rise in blood sugar, lipids and trygilicerides that increase the risk of diabetes and heart disease in later life. These are more common in overweight or obese children.

Of the SGAs, the risk of metabolic side effects is greatest with Zyprexa (olanzapine), followed by Clozaril (clozapine). Seroquel (quetiapine) and Risperdal fall into the middle. On the lower end is Abilify, Geodon (ziprasidone) and Latuda (lurasidone).

Neurological side effects

Another set of possible side effects include something called “tardive dyskinesia,” which is characterized by repetitive, involuntary movements, including facial grimaces. The risk of tardive dyskinesia increases with the dose and duration of the treatment, and it can be permanent. The risk of neurological side effects is greatest with Risperdal, Zyprexa and Abilify.

Hormonal side effects

The side effect that sparked the lawsuits against Johnson & Johnson, Risperdal’s maker, is an increase in a hormone called prolactin. Elevated prolactin is called hyperprolactinemia. Prolactin normally causes breast enlargement during pregnancy and milk secretion during breastfeeding. In girls, hyperprolactinemia can lead to breast enlargement, production of breast milk, and bone loss. In boys it can interfere with sperm production and cause breast growth, called gynecomastia.

Studies show that in kids taking antipsychotics, prolactin levels rise until around around 6 to 8 weeks (peaking at, in one study, four times higher than those treated with placebo), and then drop back toward normal. Higher doses of Risperdal — rather than longer use — appear to be linked to elevated prolactin levels.

But not all children who have elevated prolactin develop symptoms. Hyperprolactinemia is common (1.0 to 10 percent of patients develop it) but hormonal symptoms like gynecomastia are uncommon (0.1 to 1.0 percent).

Of the second-generation antipsychotics, Risperdal shows the greatest increase in prolactin levels, and Abilify the least.

Monitoring for side effects

Children taking Risperdal or another atypical antipsychotic should be monitored by their doctors regularly over the course of treatment. Before treatment begins, they should be tested to establish baselines for height, weight, vital signs, and levels of prolactin and blood fats and sugar.

Prolactin levels should be measured frequently during the first few months of treatment. If the child has elevated prolactin and shows symptoms of hyperprolactinemia, it’s recommended that the dose be tapered off and the child be switched to another SGA. If a child has elevated prolactin but shows no symptoms, it’s recommended that he continue to be monitored on a yearly basis if he is using the medication long-term, as prolonged effects of elevated prolactin on fertility and bone development are not known.

A group of Canadian researchers note that yearly lab tests with a physical exam for stable patients may seem like a waste of time to busy clinicians. But given the potential consequences, they add, “Clinicians who are unprepared to monitor children for side effects should choose not to prescribe these medications.”

Working with your doctor

As with any medication, it is important to talk to your doctor about any concerns you have. Your child’s clinician should be ready to discuss the symptoms you are seeing and explain potential options for changing dosage or medication. If you don’t feel that your child’s doctor is taking your concerns seriously, or your doctor is not following best practices for changing dosage, or adding new medications, you should get a second opinion.

If you believe your child should stop taking Risperdal, make sure you tell your doctor, and discuss the pros and cons. Don’t make adjustments or withdraw the medication without consultation. Antipsychotic medications should be reduced gradually, and the child should be monitored for side effects of withdrawing too quickly, including runny nose, diarrhea and cramping. And remember: The biggest concern to watch for is the return of dangerous behavior that the medication was prescribed to treat in the first place.

What is risperidone used for?

▪️ Psychotic illness such as schizophrenia.

▪️ To treat episodes of mania in people with the psychiatric illness, bipolar affective disorder (manic depression).

▪️ Short-term treatment of severe aggressive behaviour in elderly people with Alzheimer’s disease – if other non-drug approaches have not worked or if the person if at risk of harming themselves or others.

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Key info to know about risperidone

▪️ Risperidone can cause some people to put on weight. Talk to your doctor about this before you start treatment.

▪️ Risperidone may cause drowsiness or dizziness. If affected do not drive or operate machinery. You should avoid drinking alcohol while taking this medicine because it is likely to make any drowsiness worse.

▪️ Antipsychotic medicines can sometimes affect the ability of the body to control its core body temperature. This is more likely to be a problem in elderly people and can result in heat stroke in hot temperatures and hypothermia in cold temperatures. It is important to avoid situations that can result in you overheating or getting dehydrated.

▪️ Antipsychotic medicines are associated with an increased risk of getting a blood clot in a vein (deep vein thrombosis) or in the lungs (pulmonary embolism). For this reason, you should consult a doctor immediately if you get any of the following symptoms, which could suggest you have a blood clot: stabbing pains and/or unusual redness or swelling in one leg, pain on breathing or coughing, coughing up blood or sudden breathlessness.

▪️ Consult your doctor immediately if you experience any abnormal movements, particularly of the face, lips, jaw and tongue, while taking this medicine. These symptoms may be indicative of a rare side effect known as tardive dyskinesia, and your doctor may ask you to stop taking this medicine or decrease your dose.

▪️ Consult your doctor immediately if you experience the following symptoms while taking this medicine: high fever, sweating, muscle stiffness, faster breathing and drowsiness or sleepiness. These symptoms may be due to a rare side effect known as the neuroleptic malignant syndrome, and your treatment may need to be stopped.

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How does risperidone work?

Risperidone works in the brain, where it affects various neurotransmitters, in particular dopamine and serotonin (5HT).

Dopamine and serotonin are neurotransmitters known to be involved in regulating mood and behaviour. Psychotic illness is considered to be caused by disturbances in the activity of neurotransmitters (mainly dopamine) in the brain. Schizophrenia is known to be associated with an overactivity of dopamine in the brain, and this may be associated with the delusions and hallucinations that are a feature of this disease.

Risperidone works by blocking the receptors in the brain that dopamine acts on. This prevents the excessive activity of dopamine and helps to control schizophrenia.

Schizophrenic patients may experience ‘positive symptoms’ such as hallucinations, disturbances of thought, hostility and/or ‘negative symptoms’ such as lack of emotion and social withdrawal. Risperidone is effective in relieving both positive and negative symptoms of schizophrenia, whereas the conventional antipsychotics are usually less effective against the negative symptoms.

Risperidone also relieves ‘affective symptoms’ that are associated with schizophrenia, such as depression, guilt feelings or anxiety.

For the treatment of schizophrenia, risperidone can also be given as a depot injection that lasts for two weeks.

Risperidone: dosage instructions

▪️ The dose of risperidone that is prescribed will vary from person to person depending on the condition being treated. It is important to follow the instructions given by your doctor. These will also be printed on the dispensing label on the packet of medicine.

▪️ Risperidone tablets are usually taken once or twice a day, either with or without food.

▪️ Follow the instructions that are supplied with Risperdal liquid for measuring a dose carefully. Risperdal liquid can be taken as it is, or it may be diluted with any non-alcoholic drink except tea. When diluted in this way, the mixture should be taken immediately and not saved for later.

▪️ Risperdal consta a depot injection of risperidone is administered into the muscle of either the buttock or the upper arm, where it forms a reservoir of medicine that is slowly released into the bloodstream over a two-week period. This avoids having to take tablets every day.

▪️ If you forget to take a dose you should not take a double dose to make up for it. Just take your next dose as usual.

▪️ Unless your doctor tells you otherwise, you should not suddenly stop taking this medicine, even if you feel better and think you don’t need it any more. This is because the medicine controls the symptoms of the illness but doesn’t actually cure it. This means that if you suddenly stop treatment your symptoms could come back. Stopping the medicine suddenly may also rarely cause withdrawal symptoms such as sweating, nausea, vomiting, difficulty sleeping or tremor. When treatment with this medicine is stopped, it should be done gradually, following the instructions given by your doctor.

Who can and cannot take risperidone?

Risperidone is suitable for adults. It is not usually prescribed for children.

Risperidone is not prescribed for people with dementia that not caused by Alzheimer’s disease, for example mixed or vascular dementia.

Some people, particularly the elderly may need a lower dose of risperidone or extra monitoring. This includes the following:

  • Elderly people with Alzheimer’s dementia who are also being treated with furosemide or other strong diuretics. It is important that dehydration is avoided in these people.
  • People with liver or kidney disease.
  • People who are dehydrated.
  • People with low blood pressure or high blood pressure.
  • People with disease involving the heart and blood vessels (cardiovascular disease) for example heart failure, angina, previous heart attack or an irregular heartbeat (arrhythmia).
  • People with a very slow heart rate (bradycardia).
  • People with a personal or family history of an abnormal heart rhythm seen as a ‘prolonged QT interval’ on a heart monitoring trace or ECG.
  • People taking other medicines that can increase the risk of a ‘prolonged QT interval’
  • People with disturbances in the levels of salts (electrolytes) in their blood, especially low blood potassium or magnesium levels.
  • People with a history or risk of stroke or small temporary strokes (transient ischaemic attacks).
  • People with a personal or family history of blood clots (venous thromboembolism), for example in a vein of the leg (deep vein thrombosis) or in the lungs (pulmonary embolism).
  • People with other risk factors for getting a blood clot, for example smoking, being overweight, taking the contraceptive pill, being over 40, recent major surgery or being immobile for prolonged periods.
  • Diabetes. (If you have diabetes your blood sugar levels should be monitored closely while you are having treatment with this medicine, because it may increase your blood sugar.)
  • People with a history of seizures, eg epilepsy.
  • People with conditions that increase the risk of epilepsy or convulsions, eg brain damage or withdrawal from alcohol.
  • Parkinson’s disease.
  • People with high levels of the hormone prolactin in the blood (hyperprolactinaemia).
  • People with a tumour that is possibly dependent on prolactin, such as breast cancer.

Is risperidone safe to use during pregnancy?

The safety of this medicine during pregnancy has not been established. It should not be used in pregnancy, particularly in the first and third trimesters, unless considered essential by your doctor. If the medicine is used during the third trimester it could cause side effects or withdrawal symptoms in the baby after birth and the baby may need extra monitoring because of this.

If you do get pregnant while taking this medicine, it is important to consult your doctor straight away for advice. You should not suddenly stop taking this medicine unless your doctor tells you to, as this could cause your symptoms to come back.

Read more about how risperidone can affect you and your baby during pregnancy here.

Is risperidone safe if breastfeeding?

Risperidone passes into breast milk. The effect of this on a nursing infant are not known. It is recommended that women who need to take this medicine should not breastfeed unless the potential benefits of breastfeeding outweigh any risks to the nursing infant.

Side effects of risperidone

Medicines and their possible side effects can affect people in different ways. The following are some of the side effects that may be associated with risperidone. Just because a side effect is stated here doesn’t mean that all people taking risperidone will experience that or any side effect.

Very common (affect more than 1 in 10 people)

  • Abnormal movements of the hands, legs, face, neck and tongue, eg tremor, twitching, stiffness, rigidity, slowness or difficulty of movements (Parkinsonism or extrapyramidal effects).
  • Increased salivation.
  • Headache.
  • Difficulty sleeping (insomnia).

Related Story

Common (affect between 1 in 10 and 1 in 100 people)

  • Sleepiness, fatigue or sedation.
  • Dizziness.
  • Restlessness, agitation or anxiety.
  • Change in appetite.
  • Weight gain – see warning section above.
  • Increased level of the hormone prolactin in the blood (hyperprolactinaemia) – uncommonly this may lead to symptoms such as breast enlargement, production of breast milk and menstrual disturbances.
  • Blurred vision.
  • Inflammation of the lining of the nose (rhinitis) causing a blocked or runny nose.
  • Nosebleeds.
  • Cough or shortness of breath.
  • Dry mouth.
  • Disturbances of the gut such as constipation, diarrhoea, nausea, vomiting, indigestion or abdominal pain.
  • Swollen ankles.
  • Fast heartbeat.
  • Chest pain.
  • Fever.

Uncommon (affect between 1 in 100 and 1 in 1000 people)

  • Confusion.
  • Sexual problems such as reduced sex drive, erectile dysfunction or inability to orgasm.
  • Low blood pressure, and drops in blood pressure when moving from a lying down or sitting position to standing up that may cause dizziness or fainting.
  • Muscle or joint pain, weakness or stiffness.
  • Skin reactions such as rash, itching, hair loss, acne, discolouration, dry or flaky skin.
  • Ear pain, sensation of ringing or other noise in the ears (tinnitus).
  • Red, watery or dry eyes, conjunctivitis.
  • Problems with speech, attention, balance or co-ordination.
  • Tardive dyskinesia (see warning section above).
  • Stroke or mini-stroke.
  • Change in taste.
  • Irregular heart rhythms.
  • Awareness of your heartbeat (palpitations).
  • Increased blood glucose levels or diabetes. Tell your doctor if you notice you feel unusually hungry or thirsty, or need to pass urine more often than usual. People with diabetes should monitor their blood sugar closely.
  • Raised levels of fats called cholesterol or triglycerides in the blood.
  • Increased body temperature.
  • Pain or difficulty passing urine.
  • Excessive need to pass urine or urinary incontinence.
  • Infection of the breathing passages, such as sinusitis, flu, bronchitis.
  • Decreased numbers of red blood cells, white blood cells or platelets in the blood. You should consult your doctor if you experience any of the following symptoms: unexplained bruising or bleeding, purple spots, sore throat, mouth ulcers, high temperature (fever), feeling tired or general illness. Your doctor may want to take a blood test to check your blood cells.

Rare (affect between 1 in 1000 and 1 in 10,000 people)

  • Neuroleptic malignant syndrome.
  • Yellowing of the skin and whites of the eyes (jaundice).
  • Inflammation of the pancreas (pancreatitis).
  • Prolonged erection (priapism). If you get an erection that lasts longer than four hours while taking this medicine, you should consult a doctor immediately.
  • Breast enlargement.
  • Problem with eye movement such as rolling of the eyes.
  • Blood clot in the leg or the lungs (thromboembolism).

If you want any more information about the possible side effects of risperidone, read the leaflet provided with the medicine. You can find a copy of this here

If you think you have experienced side-effects you can report them using the yellow card scheme.

Can I take other medicines with risperidone?

While you’re taking risperidone, you should always check with your doctor or pharmacist before taking any non-prescription medicines, to make sure that the combination is safe.

Painkillers and risperidone

It’s fine to take painkillers like paracetamol, ibuprofen and aspirin with risperidone, assuming these are appropriate for you.

You’re more likely to feel sleepy and get other side effects if you take risperidone with opioid painkillers such as codeine, tramadol, morphine or fentanyl.

Medicines that cause sleepiness

You’re more likely to feel sleepy if you take risperidone with other medicines that can cause drowsiness, such as the following:

  • antihistamines that make you sleepy, such as chlorphenamine, promethazine, triprolidine, hydroxyzine, cinnarizine (some of these are found in over the counter cough, cold, hayfever and travel sickness remedies)
  • antipsychotics such as haloperidol, chlorpromazine
  • benzodiazepines, such as temazepam, diazepam, lorazepam
  • gabapentin
  • muscle relaxants, such as baclofen
  • pizotifen
  • pregabalin
  • sleeping tablets, such as zopiclone, zolpidem
  • tricyclic antidepressants, such as amitriptyline.

Medicines that affect heart rhythms

If risperidone is taking in combination with the following medicines, there may be an increased risk in abnormal heart rhythms.

  • antiarrhythmics (medicines to treat abnormal heart beats), such as amiodarone, procainamide, disopyramide, sotalol
  • the antihistamines astemizole, mizolastine or terfenadine
  • arsenic trioxide
  • atomoxetine
  • certain antidepressants, such as amitriptyline, imipramine, maprotiline
  • certain antimalarials, such as halofantrine, chloroquine, quinine, mefloquine, Riamet
  • certain other antipsychotics, such as thioridazine, haloperidol, sertindole, pimozide
  • cisapride
  • dronedarone
  • droperidol
  • intravenous erythromycin or pentamidine
  • methadone
  • moxifloxacin
  • saquinavir.

Medicines that lower blood pressure

Risperidone may enhance the blood pressure-lowering effects of medicines that lower blood pressure, including medicines used to treat high blood pressure (antihypertensives) and medicines that lower blood pressure as a side effect, such as benzodiazepines. If you are taking medicines that lower blood pressure you should tell your doctor if you feel dizzy or faint after starting treatment with this medicine, as your doses may need adjusting.

Other medicine interactions with risperidone

Diuretics such as furosemide can alter the levels of salts such as potassium in the blood, this may increase the risk of irregular heart rhythms if taken in combination with risperidone

Risperidone may oppose the effect of medicines for Parkinson’s disease that work by stimulating dopamine receptors in the brain, for example levodopa, ropinirole, pergolide, bromocriptine.

Risperidone may oppose the effect of anticonvulsant medicines used to treat epilepsy.

The following medicines may speed up the breakdown of risperidone in the body and so could make it less effective. If you take any of these medicines, your doctor may need to increase your dose of risperidone:

  • carbamazepine
  • phenytoin
  • rifampicin.

The following medicines may slow down the breakdown of risperidone in the body and so could increase the amount in the blood. If you take any of these medicines, your doctor may need to prescribe a lower dose of risperidone:

  • fluoxetine
  • paroxetine
  • verapamil.

Read more detailed information about medicines that may interact with risperidone here

Related Story

Last updated 09/10/2019

Rita Ghelani (BPharm, MRPharmS) Pharmacist A UK registered practising pharmacist with over 20 years’ experience, Rita is a member of the medical journalists’ association (MJA) and has a wealth of experience in community pharmacy.

Risperidone for psychological disorders

This leaflet is about the use of risperidone in autism, attention deficit hyperactivity disorder (often shortened to ADHD) bipolar disorder, Tourette’s syndrome, schizophrenia and learning disability.

This leaflet has been written specifically for parents and carers about the use of this medicine in children. The information may differ from that provided by the manufacturer. Please read this leaflet carefully. Keep it somewhere safe so that you can read it again.

Do not stop giving risperidone suddenly, as your child is likely to get withdrawal symptoms.

Name of drug

Brand names: Risperdal®, Quicklet®

Why is it important for my child to take this medicine?

Risperidone belongs to the group of medicines called antipsychotics. It works by changing the activity of chemicals in the brain called neurotransmitters and will affect your child’s mood and psychological behaviour.

What is risperidone available as?

  • Tablets: 500 micrograms, 1 mg, 2 mg, 3 mg, 4 mg, 6 mg; these contain lactose
  • Orodispersible tablets: 500 micrograms, 1 mg, 2 mg, 3 mg, 4 mg; these contain aspartame
  • Liquid medicine: 5 mg in 5 mL

When should I give risperidone?

Risperidone may be given once or twice each day. Your doctor will tell you how often to give it.

  • Once a day: this is usually in the evening.
  • Twice a day: this should be once in the morning and once in the evening. Ideally these times are 10–12 hours apart, for example some time between 7 and 8 am, and between 7 and 8 pm.

Give the medicine at about the same time(s) each day so that this becomes part of your child’s daily routine, which will help you to remember.

How much should I give?

Your doctor will work out the amount of risperidone (the dose) that is right for your child. The dose will be shown on the medicine label. Your doctor will give your child a low dose to start with. They may then increase the dose as your child gets used to the medicine and depending on how your child responds to it.

It is important that you follow your doctor’s instructions about how much to give.

How should I give it?

Tablets should be swallowed with a glass of water, milk or juice. Your child should not chew the tablet.

Orodispersible tablets are designed to dissolve in the mouth. Place the tablet on your child’s tongue. It should stay there until it has dissolved (which usually takes about a minute), or your child can suck the tablet gently. Your child can then swallow the dissolved tablet.

Liquid medicine: Measure out the right amount using a medicine spoon or oral syringe. You can get these from your pharmacist. Do not use a kitchen teaspoon as it will not give the right amount.

To hide the taste of the liquid medicine, you can add the dose into a small amount of milk or fruit juice. Do not add it to hot drinks. Your child should drink all the mixture straight away.

When should the medicine start working?

It may take a few days or weeks for risperidone to work properly, depending on what you child is being treated for, so your child may still have symptoms for a while. Continue to give the medicine to your child during this time. Your doctor will decide whether it is helping once your child has been taking it for a few weeks.

What if my child is sick (vomits)?

  • If your child is sick less than 30 minutes after having a dose of risperidone, give them the same dose again.
  • If your child is sick more than 30 minutes after having a dose of risperidone, you do not need to give them another dose. Wait until the next normal dose.

What if I forget to give it?

Do not give the missed dose. Wait until the next normal dose, and then continue to give the medicine as usual.

Never give a double dose of risperidone.

If you have missed more than one dose, contact your doctor for advice.

What if I give too much?

It may be dangerous to give too much risperidone.

If you think you may have given your child too much risperidone, contact your doctor or NHS Direct (0845 4647 in England and Wales; 08454 24 24 24 in Scotland) or take your child to hospital.

Take the medicine container or packaging with you, even if it is empty. This will be useful to the doctor. Have the medicine or packaging with you if you telephone for advice.

Are there any possible side-effects?

We use medicines to make our children better, but sometimes they have other effects that we don’t want (side-effects).

Side-effects you must do something about

If your child feels faint or dizzy, or seems to be losing consciousness, has a fever (temperature above 38°C), is cold and sweaty, has a weak or rapid heart rate (they may feel as though their heart is racing or fluttering) and stiff muscles, they may be having a rare reaction to risperidone. Contact your doctor or take your child to hospital or call an ambulance straight away.

Your child may start to have some unusual muscle movements they have not had before, such as muscle spasm, twitching in the jaw, tongue or face and body, slow movements, shaking or stiffness. Contact your doctor as soon as possible.

Other side-effects you need to know about

Your child may:

  • feel dizzy or light-headed when they stand up, or may faint. Encourage them to stand up slowly, and to sit or lie down if they feel dizzy or light-headed
  • feel drowsy (sleepy). This will cause fewer problems if they have risperidone in the evening. If your child also takes risperidone during the day, remember that they may not be alert
  • get stomach ache or constipation (difficulty doing a poo), feel sick (nausea) or be sick (vomit). If this is still a problem after 2 weeks, contact your doctor
  • get a headache, become anxious or have sleep disturbances such as difficulty getting to sleep. Some children find their eyesight is blurry or double
  • have nosebleeds or develop a rash
  • have more saliva, a dry mouth, or an increased appetite. Encourage them to eat fruit and vegetables and low-calorie foods, rather than foods that contain a lot of calories (avoid crisps, cakes, biscuits and sweets) and to have plenty of physical activity. Otherwise they may put on weight.

Contact your doctor if you are worried about any of these side-effects.

  • Girls may find their periods become irregular or stop or that they have swelling, soreness or leakage from their breasts. Boys may also feel sore around the breast area. Tell your doctor about these symptoms at your next visit.

There may, sometimes, be other side-effects that are not listed above. If you notice anything unusual and are concerned, contact your doctor.

Can other medicines be given at the same time as risperidone?

  • You can give your child medicines that contain paracetamol or ibuprofen, unless your doctor has told you not to.
  • Risperidone should not be taken with some medicines that you get on prescription. Tell your doctor and pharmacist about any other medicines your child is taking before giving risperidone.
  • Check with your doctor or pharmacist before giving any other medicines to your child. This includes herbal or complementary medicines.

Is there anything else I need to know about this medicine?

Do not stop giving risperidone suddenly, as your child may get withdrawal effects and feel unwell. If you or your child wants to stop taking risperidone, discuss this with your doctor. They will explain how to reduce the dose bit by bit.

Do not change the dose of risperidone that you give your child without discussing this with your doctor.

General advice about medicines

  • Try to give medicines at about the same time(s) each day, to help you remember.
  • If you are not sure a medicine is working, contact your doctor but continue to give the medicine as usual in the meantime. Do not give extra doses, as you may do harm.
  • Only give this medicine to your child. Never give it to anyone else, even if their condition appears to be the same, as this could do harm.

If you think someone else may have taken the medicine by accident, contact your doctor straight away.

  • Make sure that you always have enough medicine. Order a new prescription at least 2 weeks before you will run out.
  • Make sure that the medicine you have at home has not reached the ‘best before’ or ‘use by’ date on the packaging. Give old medicines to your pharmacist to dispose of.

Where should I keep this medicine?

  • Keep the medicine in a cupboard, away from heat and direct sunlight. It does not need to be kept in the fridge.
  • Make sure that children cannot see or reach the medicine.
  • Keep the medicine in the container it came in.

Who to contact for more information

Your doctor, pharmacist or nurse will be able to give you more information about risperidone and about other medicines used for children with autism, ADHD, bipolar disorder, Tourette’s syndrome, schizophrenia or learning disability.

Anxiety disorders are a heterogeneous spectrum whose diagnostic criteria continue to evolve. With the DSM-5, anxiety disorders, trauma- and stressor-related disorders, and obsessive-compulsive and related disorders have been separated into a separate classification schema.

Among other changes, the DSM-5 also added a symptom cluster for “negative alterations in cognition and mood” to the criteria for post-traumatic stress disorder, separated agoraphobia from panic disorder criteria, changed the specifier option within social anxiety disorder, and defined several new disorders in the obsessive-compulsive subset.1

Similarly, there is increasing evidence for a broad spectrum of treatment responses, both to pharmacologic and non-pharmacologic modalities, across anxiety diagnoses. This diversity is evident when discussing antipsychotic efficacy. The list of anxiety diagnoses with demonstrated efficacy from antipsychotics is much narrower than the list of anxiety disorders showing benefit from selective serotonin reuptake inhibitors (SSRIs), for example.

The risks of metabolic side effects, as well as the sequelae of the dopamine blockade, can significantly impact morbidity and mortality, limiting the utility of antipsychotics. No antipsychotic has yet garnered an FDA indication for an anxiety disorder and the studies cited in the remainder of this article will focus on treatment of adults.

Cognitive-behavioral therapy (CBT) has robust, first-line evidence for treating obsessive-compulsive disorder (OCD).2 When pharmacology is employed, the usual first step is an SSRI. When OCD is refractory to an initial trial with an SSRI, the next step is still not augmentation with an antipsychotic. Clomipramine, for example, may beat SSRIs in monotherapy trials for OCD.3

Many clinicians, appropriately, try several monotherapy trials of different antidepressants before considering augmentation. Even if augmentation of an SSRI is ultimately considered, antipsychotics may not be the first choice, given evidence that augmentation with CBT is superior to augmentation with antipsychotics.4

That said, there are now meta-analyses that support eventual consideration of antipsychotic augmentation in algorithms for refractory OCD.5 The lack of head-to-head trials makes it difficult to come to a firm, evidence-based recommendation on which antipsychotic is the most efficacious. However, the risperidone studies, when grouped together, are particularly convincing.

Of the studies included in the Dold, et al meta-analysis, the two, placebo-controlled, risperidone augmentation trials that employed flexible dosing suggested efficacy at 2mg to 3mg per day.6,7 However, efficacy has also been seen with doses as low as 0.5mg per day.8 Compared to the many other treatment modalities that demonstrate benefit for OCD, risperidone conveys higher rates of, amongst other things, significant metabolic and dopamine blockade side effects. Certain dopamine blockade side effects, such as tardive dyskinesia, can be irreversible. These factors of comparative efficacy and side effects make risperidone less likely to be considered in OCD treatment algorithms.9

While antipsychotic studies of OCD most often employ a strategy of augmentation, trials of quetiapine for generalized anxiety disorder (GAD) have often been designed to study the medication as monotherapy. There have been enough trials of quetiapine monotherapy to enable the construction of meta-analyses that confirm the efficacy of the drug in GAD.10 However, quetiapine monotherapy does not appear to be more efficacious than SSRI monotherapy in head-to-head trials.11

There are also a number of other interventions with positive, placebo-controlled evidence for GAD. Venlafaxine and duloxetine both have FDA approval for GAD. The azapirones, of which buspirone is an example, have positive, placebo-controlled data.12 Though not FDA-approved for GAD, pregabalin has positive, placebo-controlled data.13

CBT can also be effective for GAD.14 Compared to many other interventions, quetiapine has a more significant side effect profile. Thus, despite the evidence of efficacy, quetiapine does not appear amongst the first choices of pharmacologic interventions in GAD treatment algorithms.15

Risperdal and olanzapine have been studied in post-traumatic stress disorder (PTSD), using DSM-IV diagnostic criteria. Some of these augmentation and monotherapy studies have demonstrated modest efficacy, though the results have been variable and meta-analyses have only been able to document a small effect size.16 The metabolic side effects, however, were evident.

However, there are studies where antipsychotics do not demonstrate efficacy over placebo.17 In light of the many other effective pharmacologic and psychological interventions for PTSD, the side effect profile of antipsychotics can be prohibitive. Antipsychotics are not first or second-line pharmacologic interventions for PTSD.9 Moreover, the overall data for antipsychotic efficacy, target PTSD symptom cluster, and target patient sub-population remains poorly defined.

Quetiapine does not appear to be effective for SAD.18 In the absence of co-occurring bipolar disorder, there have been no placebo-controlled trials of antipsychotics in panic disorder.

Though SSRIs are considered amongst the first-line pharmacologic options for OCD, GAD, SAD, PTSD, and panic disorder, the antipsychotics do not enjoy the same breadth of support. With varying degrees of evidence, antipsychotics do appear on treatment algorithms for several anxiety disorders, but not in the top tiers.

Ryan Kimmel, MD, is Assistant Professor in the Department of Psychiatry & Behavioral Sciences at the University of Washington School of Medicine.

  1. American Psychiatric Association. DSM-5 Task Force. Diagnostic and statistical manual of mental disorders : DSM-5 (5th ed.). 2013. Washington, D.C.: American Psychiatric Association.
  2. Foa EB, et al. “Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder.” Am J Psychiatry. 2005; 162(1): 151-161.
  3. Greist JH, et al. “Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. A meta-analysis.” Arch Gen Psychiatry. 2005; 52(1): 53-60.
  4. Simpson HB, et al. “Cognitive-behavioral therapy vs risperidone for augmenting serotonin reuptake inhibitors in obsessive-compulsive disorder: a randomized clinical trial.” JAMA Psychiatry. 2013; 70(11): 1190-1199.
  5. Dold M, et al. Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a meta-analysis of double-blind, randomized, placebo-controlled trials. Int J Neuropsychopharmacol. 2013; 16(3): 557-574.
  6. Hollander E, et al. “Risperidone augmentation in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study.” Int J Neuropsychopharmacol. 2003; 6(4): 397-401.
  7. McDougle CJ, et al. “A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder.” Arch Gen Psychiatry. 2000; 57(8): 794-801.
  8. Erzegovesi S. “Low-dose risperidone augmentation of fluvoxamine treatment in obsessive-compulsive disorder: a double-blind, placebo-controlled study.” Eur Neuropsychopharmacol. 2005; 15(1): 69-74.
  9. Katzman MA, et al. “Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders”. BMC Psychiatry. 2014; 14 Suppl 1: S1.
  10. Maher, AR, et al. “Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults: a systematic review and meta-analysis.” JAMA. 2011; 306(12): 1359-1369.
  11. Merideth C, et al. “Efficacy and tolerability of extended release quetiapine fumarate monotherapy in the acute treatment of generalized anxiety disorder: a randomized, placebo controlled and active-controlled study.” Int Clin Psychopharmacol. 2012; 27(1): 40-54.
  12. Chessick CA, et al. “Azapirones for generalized anxiety disorder.” Cochrane Database Syst Rev. 2006; (3): CD006115.
  13. Rickels K, et al. “Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam.” Arch Gen Psychiatry. 2005; 62(9): 1022-1030.
  14. Cuijpers P, et al. “Psychological treatment of generalized anxiety disorder: a meta-analysis.” Clin Psychol Rev. 2014; 34(2): 130-140.
  15. Linden M, et al. “The best next drug in the course of generalized anxiety disorders: the “PN-GAD-algorithm”. Int J Psychiatry Clin Pract. 2013; 17(2): 78-89.
  16. Ahearn EP, et al. “A review of atypical antipsychotic medications for posttraumatic stress disorder.” Int Clin Psychopharmacol. 2011; 26(4): 193-200.
  17. Krystal JH, et al. “Adjunctive risperidone treatment for antidepressant-resistant symptoms of chronic military service-related PTSD: a randomized trial.” JAMA. 2011; 306(5): 493-502.
  18. Depping AM, et al. “Second-generation antipsychotics for anxiety disorders.” Cochrane Database Syst Rev. 2010; (12): CD008120.

Treatment-resistant depression: Are atypical antipsychotics effective and safe enough?

Adding second-generation antipsychotics (SGAs) may boost the effectiveness of antidepressants in treatment-resistant unipolar major depression. Exactly when to try SGAs remains unclear, however, given their potential for adverse effects.

Major depression often is severe and chronic, and many patients remain ill even after multiple rounds of treatment. For patients without psychosis, where do SGAs fit into an algorithm for treatment-resistant depression?

This article examines the evidence on antipsychotic augmentation and discusses issues to consider—effectiveness, adverse effects, therapeutic dosages, and the patient’s quality of life—in making your clinical decisions.

Antidepressants alone

An optimal trial. Most depressed patients do not experience full response after initial antidepressant treatment, even with optimal therapeutic trials. An optimal trial means maintaining the maximum tolerated dosage within the antidepressant’s typical therapeutic range for at least 3 weeks.1 Reported remission rates from initial and second-line treatments include:

  • one-third of patients after a vigorous initial trial of citalopram in a National Institute of Mental Health study2
  • 20% to 30% of patients given citalopram plus bupropion or buspirone3 or switched to bupropion, sertraline, or venlafaxine4
  • 50% of patients treated for depression in a primary care practice during the first 2 years after an initial antidepressant prescription.5

Among patients who do achieve remission from initial therapy, many eventually relapse to major depression or show a recurrence of depressive symptoms.6

Subsequent options. In addition to various monotherapies and combinations, many options have been proposed for managing nonresponse to initial antidepressant therapy (Table 1). These include:

  • augmenting with lithium, thyroid hormone, pindolol, or estrogen
  • switching to a drug in another therapeutic class, such as a tricyclic antidepressant or monoamine oxidase inhibitor
  • adding cognitive-behavioral therapy.7

Yet many patients remain depressed after these treatments are tried, with a reduced quality of life and at high risk for suicide or long-term disability (Box 1).6,8 For these patients, accumulating evidence suggests that at least some SGAs can be effective for acute treatment of unipolar depression that does not respond to antidepressants.

Box 1

Remission: Why it’s the goal of antidepressant therapy

Depression is often chronic and disabling. Selective serotonin reuptake inhibitors (SSRIs) are the mainstay of treatment, but recent data suggest that:

  • few patients achieve therapeutic remission with initial SSRIs
  • relapse or recurrence after remission is common.6

Clinically, this means psychiatrists contend with treatment resistance in nearly all patients with major depression.

Chronic, inadequately treated depression has a pervasive, adverse effect on patients’ quality of life, impairing the ability to work and perform social roles such as parenting. Even when an antidepressant produces partial response, considerable impairment remains. Depressed patients who do not achieve full therapeutic remission remain in this partially remitted, disabled state throughout treatment.8

Aggressive and persistent management is the key to effectively treating major depression.

Table 1

Therapeutic suggestions when an SSRI does not lead to remission*

Pharmacotherapy Example Recommended dosing
Monotherapy An SNRI such as:
Duloxetine 30 to 120 mg/d
Venlafaxine XR 150 to 375 mg/d
Combination therapies with SSRIs Bupropion 200 to 400 mg/d
Buspirone 30 to 60 mg/d
Augmentation Lithium 900 to 1,200 mg/d
Thyroid hormone 25 mcg/d
Pindolol 5 to 30 mg bid
Estrogen (such as 17a-estradiol) 100 mcg/d
Switch to another Tricyclic antidepressant class Tricyclic
Imipramine 150 to 250 mg/d*
Nortriptyline 75 to 200 mg/d*
Desipramine 150 to 250 mg/d*
Phenelzine 30 to 60 mg/d
Tranylcypromine 20 to 60 mg/d
Selegiline (patch) 9 to 12 mg/patch/day
* Suggestions are not listed in stepwise order
MAOI: monoamine oxidase inhibitor
SNRI: serotonin-norepinephrine reuptake inhibitor
SSRI: selective serotonin reuptake inhibitor

Atypicals for unipolar depression

Why atypicals? Researchers are investigating the use of SGAs in treatment-resistant mood disorders because of these drugs’ unique psychopharmacologic properties (Box 2).9-11

Except for clozapine, all available SGAs—aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone—are FDA-approved for acute bipolar mania. Evidence also strongly supports the benefits of quetiapine12 and the fixed-dose olanzapine/ fluoxetine combination13 for bipolar depression. Olanzapine/fluoxetine—originally studied for use in treatment-resistant unipolar depression—is approved for bipolar depression.14

Robust response. An uncontrolled case series first suggested that an SGA might help treat unipolar depression after initial selective serotonin reuptake inhibitors (SSRIs) fail to achieve remission. Ostroff and Nelson15 enrolled 8 outpatients (5 men, 3 women, ages 36 to 75) with nonpsychotic unipolar major depression that did not respond to initial fluoxetine or paroxetine. Patients had been taking fluoxetine, 20 to 40 mg/d, for 6 weeks to 4 months or paroxetine, 10 to 30 mg/d, for 2 to 8 weeks.

Patients reported a robust clinical effect within days after risperidone, 0.5 to 1.0 mg/d, was added to the SSRIs. Depression symptoms dropped to remission levels within 1 week, as measured by baseline and follow-up Hamilton Rating Scale for Depression (HAM-D) scores.

Olanzapine/fluoxetine. Our group subsequently enrolled 28 nonpsychotic patients with unipolar depression in a double-blind, placebo-controlled trial.14 We first treated these patients—who had not responded adequately to an SSRI or an antidepressant from another class—with open-label fluoxetine, up to 60 mg/d. Those whose scores on depression rating scales improved by ≥30% were excluded from the double-blind phase, when we randomly assigned the remaining patients to:

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