Topiramate for weight loss




The following serious adverse reactions are discussed in more detail in other sections of the labeling:

  • Acute Myopia and Secondary Angle Closure Glaucoma
  • Visual Field Defects
  • Oligohidrosis and Hyperthermia
  • Metabolic Acidosis
  • Suicidal Behavior and Ideation
  • Cognitive/Neuropsychiatric Adverse Reactions
  • Hyperammonemia and Encephalopathy (Without and With Concomitant Valproic Acid Use)
  • Kidney Stones
  • Hypothermia with Concomitant Valproic Acid (VPA) Use

The data described in the following sections were obtained using TOPAMAX® Tablets.

Clinical Trials Experience

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

Monotherapy Epilepsy

Adults 16 Years of Age and Older

The most common adverse reactions in the controlled clinical trial that occurred in adults in the 400 mg/day TOPAMAX® group and at an incidence higher (≥ 10 %) than in the 50 mg/day group were: paresthesia, weight loss and anorexia (see Table 5).

Approximately 21% of the 159 adult patients in the 400 mg/day group who received TOPAMAX® as monotherapy in the controlled clinical trial discontinued therapy due to adverse reactions. The most common (≥ 2% more frequent than low-dose 50 mg/day TOPAMAX®) adverse reactions causing discontinuation were difficulty with memory, fatigue, asthenia, insomnia, somnolence, and paresthesia.

Pediatric Patients 6 to 15 Years of Age

The most common adverse reactions in the controlled clinical trial that occurred in pediatric patients in the 400 mg/day TOPAMAX® group and at an incidence higher (≥10%) than in the 50 mg/day group were fever and weight loss (see Table 5).

Approximately 14% of the 77 pediatric patients in the 400 mg/day group who received TOPAMAX® as monotherapy in the controlled clinical trial discontinued therapy due to adverse reactions. The most common (≥2% more frequent than low-dose 50 mg/day TOPAMAX®) adverse reactions resulting in discontinuation were difficulty with concentration/attention, fever, flushing, and confusion.

Table 5 presents the incidence of adverse reactions occurring in at least 3% of adult and pediatric patients treated with 400 mg/day TOPAMAX® and occurring with greater incidence than 50 mg/day TOPAMAX®.

Table 5: Adverse Reactions in the High Dose Group As Compared to the Low Dose Group, in Monotherapy Epilepsy Trials in Adult and Pediatric Patients

Body System
Adverse Reaction
Age Group
(6 to 15 Years)
(Age ≥16 Years)
TOPAMAX® Daily Dosage Group (mg/day)
50 400 50 400
(N=74) % (N=77) % (N=160) % (N=159) %
Body as a Whole – General Disorders
Asthenia 0 3 4 6
Fever 1 12
Leg pain 2 3
Central & Peripheral Nervous System Disorders
Paresthesia 3 12 21 40
Dizziness 13 14
Ataxia 3 4
Hypoesthesia 4 5
Hypertonia 0 3
Involuntary muscle contractions 0 3
Vertigo 0 3
Gastro-Intestinal System Disorders
Constipation 1 4
Diarrhea 8 9
Gastritis 0 3
Dry mouth 1 3
Liver and Biliary System Disorders
Increase in Gamma-GT 1 3
Metabolic and Nutritional Disorders
Weight loss 7 17 6 17
Platelet, Bleeding & Clotting Disorders
Epistaxis 0 4
Psychiatric Disorders
Anorexia 4 14
Anxiety 4 6
Cognitive problems 1 6 1 4
Confusion 0 3
Depression 0 3 7 9
Difficulty with concentration or attention 7 10 7 8
Difficulty with memory 1 3 6 11
Insomnia 8 9
Decrease in libido 0 3
Mood problems 1 8 2 5
Personality disorder (behavior problems) 0 3
Psychomotor slowing 3 5
Somnolence 10 15
Red Blood Cell Disorders
Anemia 1 3
Reproductive Disorders, Female
Intermenstrual bleeding 0 3
Vaginal hemorrhage 0 3
Resistance Mechanism Disorders
Infection 3 8 2 3
Viral infection 3 6 6 8
Respiratory System Disorders
Bronchitis 1 5 3 4
Upper respiratory tract infection 16 18
Rhinitis 5 6 2 4
Sinusitis 1 4
Skin and Appendages Disorders
Alopecia 1 4 3 4
Pruritus 1 4
Rash 3 4 1 4
Acne 2 3
Special Senses Other, Disorders
Taste perversion 3 5
Urinary System Disorders
Cystitis 1 3
Micturition frequency 0 3
Renal calculus 0 3
Urinary incontinence 1 3
Vascular (Extracardiac) Disorders
Flushing 0 5

Adjunctive Therapy Epilepsy

In pooled controlled clinical trials in adults with partial onset seizures, primary generalized tonicclonic seizures, or Lennox-Gastaut syndrome, 183 patients received adjunctive therapy with TOPAMAX® at dosages of 200 to 400 mg/day (recommended dosage range) and 291 patients received placebo. Patients in these trials were receiving 1 to 2 concomitant antiepileptic drugs in addition to TOPAMAX® or placebo.

The most common adverse reactions in the controlled clinical trial that occurred in adult patients in the 200-400 mg/day TOPAMAX® group with an incidence higher (≥ 10 %) than in the placebo group were: dizziness, speech disorders/related speech problems, somnolence, nervousness, psychomotor slowing, and vision abnormal (Table 6).

Table 6 presents the incidence of adverse reactions occurring in at least 3% of adult patients treated with 200 to 400 mg/day TOPAMAX® and was greater than placebo incidence. The incidence of some adverse reactions (e.g., fatigue, dizziness, paresthesia, language problems, psychomotor slowing, depression, difficulty with concentration/attention, mood problems) was dose-related and much greater at higher than recommended TOPAMAX® dosing (i.e., 600 mg – 1000 mg daily) compared to the incidence of these adverse reactions at the recommended dosing (200 mg to 400 mg daily) range.

Table 6: Most Common Adverse Reactions in Pooled Placebo-Controlled, Add-On Epilepsy Trials in Adultsa

Body System
Adverse Reaction
Placebo TOPAMAX®
Dosage (mg/day)
(N=291) (N=183)
Body as a Whole-General Disorders
Fatigue 13 15
Asthenia 1 6
Back pain 4 5
Chest pain 3 4
Influenza-like symptoms 2 3
Central & Peripheral Nervous System Disorders
Dizziness 15 25
Ataxia 7 16
Speech disorders/Related speech problems 2 13
Paresthesia 4 11
Nystagmus 7 10
Tremor 6 9
Language problems 1 6
Coordination abnormal 2 4
Gait abnormal 1 3
Gastro-Intestinal System Disorders
Nausea 8 10
Dyspepsia 6 7
Abdominal pain 4 6
Constipation 2 4
Metabolic and Nutritional Disorders
Weight loss 3 9
Psychiatric Disorders
Somnolence 12 29
Nervousness 6 16
Psychomotor slowing 2 13
Difficulty with memory 3 12
Anorexia 4 10
Confusion 5 11
Difficulty with concentration/attention 2 6
Mood problems 2 4
Agitation 2 3
Aggressive reaction 2 3
Emotional lability 1 3
Cognitive problems 1 3
Breast pain 2 4
Respiratory System Disorders
Pharyngitis 2 6
Rhinitis 6 7
Sinusitis 4 5
Vision Disorders
Vision abnormal 2 13
Diplopia 5 10
a Patients in these add-on/adjunctive trials were receiving 1 to 2 concomitant antiepileptic drugs in addition to TOPAMAX® or placebo.

In controlled clinical trials in adults, 11% of patients receiving TOPAMAX® 200 to 400 mg/day as adjunctive therapy discontinued due to adverse reactions. This rate appeared to increase at dosages above 400 mg/day. Adverse reactions associated with discontinuing TOPAMAX® included somnolence, dizziness, anxiety, difficulty with concentration or attention, fatigue, and paresthesia and increased at dosages above 400 mg/day.

Pediatric Patients 2 to 15 Years of Age

In pooled, controlled clinical trials in pediatric patients (2 to 15 years of age) with partial onset seizures, primary generalized tonic-clonic seizures, or Lennox-Gastaut syndrome, 98 patients received adjunctive therapy with TOPAMAX® at dosages of 5 to 9 mg/kg/day (recommended dose range) and 101 patients received placebo.

The most common adverse reactions in the controlled clinical trial that occurred in pediatric patients in the 5 mg to 9 mg/kg/day TOPAMAX® group with an incidence higher (≥ 10 %) than in the placebo group were: fatigue and somnolence (Table 7).

Table 7 presents the incidence of adverse reactions that occurred in at least 3% of pediatric patients 2 to 15 years of age receiving 5 mg to 9 mg/kg/day (recommended dose range) of TOPAMAX® and was greater than placebo incidence.

Table 7: Adverse Reactions in Pooled Placebo-Controlled, Add-On Epilepsy Trials in Pediatric Patients 2 to 15 Years of Agea,b

Body System/
Adverse Reaction
Body as a Whole – General Disorders
Fatigue 5 16
Injury 13 14
Central & Peripheral Nervous System Disorders
Gait abnormal 5 8
Ataxia 2 6
Hyperkinesia 4 5
Dizziness 2 4
Speech disorders/Related speech problems 2 4
Gastro-Intestinal System Disorders
Nausea 5 6
Saliva increased 4 6
Constipation 4 5
Gastroenteritis 2 3
Metabolic and Nutritional Disorders
Weight loss 1 9
Platelet, Bleeding, & Clotting Disorders
Purpura 4 8
Epistaxis 1 4
Psychiatric Disorders
Somnolence 16 26
Anorexia 15 24
Nervousness 7 14
Personality disorder (behavior problems) 9 11
Difficulty with concentration/attention 2 10
Aggressive reaction 4 9
Insomnia 7 8
Difficulty with memory 0 5
Confusion 3 4
Psychomotor slowing 2 3
Resistance Mechanism Disorders
Infection viral 3 7
Respiratory System Disorders
Pneumonia 1 5
Skin and Appendages Disorders
Skin disorder 2 3
Urinary System Disorders
Urinary incontinence 2 4
a Patients in these add-on/adjunctive trials were receiving 1 to 2 concomitant antiepileptic drugs in addition to TOPAMAX® or placebo.
b Values represent the percentage of patients reporting a given adverse reaction. Patients may have reported more than one adverse reaction during the study and can be included in more than one adverse reaction category.

None of the pediatric patients who received TOPAMAX® adjunctive therapy at 5 to 9 mg/kg/day in controlled clinical trials discontinued due to adverse reactions.



In the four multicenter, randomized, double-blind, placebo-controlled, parallel group migraine prophylaxis clinical trials (which included 35 pediatric patients 12 to 15 years of age), most adverse reactions occurred more frequently during the titration period than during the maintenance period.

The most common adverse reactions with TOPAMAX® 100 mg in migraine prophylaxis clinical trials of predominantly adults that were seen at an incidence higher (≥ 5 %) than in the placebo group were: paresthesia, anorexia, weight loss, taste perversion, diarrhea, difficulty with memory, hypoesthesia, and nausea (see Table 8).

Table 8 includes those adverse reactions that occurred in the placebo-controlled trials where the incidence in any TOPAMAX® treatment group was at least 3% and was greater than that for placebo patients. The incidence of some adverse reactions (e.g., fatigue, dizziness, somnolence, difficulty with memory, difficulty with concentration/attention) was dose-related and greater at higher than recommended TOPAMAX® dosing (200 mg daily) compared to the incidence of these adverse reactions at the recommended dosing (100 mg daily).

Table 8: Adverse Reactions in Pooled, Placebo-Controlled, Migraine Trials in Adultsa,b

Body System/
Adverse Reaction
TOPAMAX® Dosage (mg/day)
Body as a Whole-General Disorders
Fatigue 11 14 15
Injury 7 9 6
Central & Peripheral Nervous System Disorders
Paresthesia 6 35 51
Dizziness 10 8 9
Hypoesthesia 2 6 7
Language problems 2 7 6
Gastro-Intestinal System Disorders
Nausea 8 9 13
Diarrhea 4 9 11
Abdominal pain 5 6 6
Dyspepsia 3 4 5
Dry mouth 2 2 3
Gastroenteritis 1 3 3
Metabolic and Nutritional Disorders
Weight loss 1 6 9
Musculoskeletal System Disorders
Arthralgia 2 7 3
Psychiatric Disorders
Anorexia 6 9 15
Somnolence 5 8 7
Difficulty with memory 2 7 7
Insomnia 5 6 7
Difficulty with concentration/attention 2 3 6
Mood problems 2 3 6
Anxiety 3 4 5
Depression 4 3 4
Nervousness 2 4 4
Confusion 2 2 3
Psychomotor slowing 1 3 2
Reproductive Disorders, Female
Menstrual disorder 2 3 2
Reproductive Disorders, Male
Ejaculation premature 0 3 0
Resistance Mechanism Disorders
Viral infection 3 4 4
Respiratory System Disorders
Upper respiratory tract infection 12 13 14
Sinusitis 4 10 6
Pharyngitis 4 5 6
Coughing 2 2 4
Bronchitis 2 3 3
Dyspnea 2 1 3
Skin and Appendages Disorders
Pruritis 2 4 2
Special Sense Other, Disorders
Taste perversion 1 15 8
Urinary System Disorders
Urinary tract infection 2 4 2
Vision Disorders
Blurred visionc 2 4 2
a Includes 35 adolescent patients age 12 to 15 years.
b Values represent the percentage of patients reporting a given adverse reaction. Patients may have reported more than one adverse reaction during the study and can be included in more than one adverse reaction category.
c Blurred vision was the most common term considered as vision abnormal. Blurred vision was an included term that accounted for >50% of reactions coded as vision abnormal, a preferred term.

Patients treated with TOPAMAX® experienced mean percent reductions in body weight that were dose-dependent. This change was not seen in the placebo group. Mean changes of 0%, -2%, -3%, and -4% were seen for the placebo group, TOPAMAX® 50, 100, and 200 mg groups, respectively.

Pediatric Patients 12 to 17 Years of Age

In five, randomized, double-blind, placebo-controlled, parallel group migraine prophylaxis clinical trials, most adverse reactions occurred more frequently during the titration period than during the maintenance period. Among adverse reactions with onset during titration, approximately half persisted into the maintenance period.

In four, fixed-dose, double-blind migraine prophylaxis clinical trials in TOPAMAX®-treated pediatric patients 12 to 17 years of age, the most common adverse reactions with TOPAMAX® 100 mg that were seen at an incidence higher (≥5%) than in the placebo group were: paresthesia, upper respiratory tract infection, anorexia, and abdominal pain (see Table 9). Table 9 shows adverse reactions from the pediatric trial (Study 12 ) in which 103 pediatric patients were treated with placebo or 50 mg or 100 mg of TOPAMAX®, and three predominantly adult trials in which 49 pediatric patients (12 to 17 years of age) were treated with placebo or 50 mg, 100 mg or 200 mg of TOPAMAX®. Table 9 also shows adverse reactions in pediatric patients in the controlled migraine trials when the incidence in a TOPAMAX® dose group was at least 5 % or higher and greater than the incidence of placebo. Many adverse reactions shown in Table 9 indicate a dose-dependent relationship. The incidence of some adverse reactions (e.g., allergy, fatigue, headache, anorexia, insomnia, somnolence, and viral infection) was dose-related and greater at higher than recommended TOPAMAX® dosing (200 mg daily) compared to the incidence of these adverse reactions at the recommended dosing (100 mg daily).

Table 9: Adverse Reactions in Pooled Double-Blind Migraine Prophylaxis Studies in Pediatric Patients 12 to 17 Years of Agea,b,c

Body System/
Adverse Reaction
Placebo (N=45)
50 mg/day (N=46)
100 mg/day (N=48)
Body as a Whole – General Disorders
Fatigue 7 7 8
Fever 2 4 6
Central & Peripheral Nervous System Disorders
Paresthesia 7 20 19
Dizziness 4 4 6
Gastrointestinal System Disorders
Abdominal pain 9 7 15
Nausea 4 4 8
Metabolic and Nutritional Disorders
Weight loss 2 7 4
Psychiatric Disorders
Anorexia 4 9 10
Insomnia 2 9 2
Somnolence 2 2 6
Resistance Mechanism Disorders
Infection viral 4 4 8
Respiratory System Disorders
Upper respiratory tract infection 11 26 23
Rhinitis 2 7 6
Sinusitis 2 9 4
Coughing 0 7 2
Special Senses Other, Disorders
Taste perversion 2 2 6
Vision Disorders
Conjunctivitis 4 7 4
a 35 adolescent patients aged 12 to <16 years were also included in adverse reaction assessment for adults (Tables 10 and 11)
b Incidence is based on the number of subjects experiencing at least 1 adverse event, not the number of events.
c Included studies MIG-3006, MIGR-001, MIGR-002 and MIGR-003

In the double-blind placebo-controlled studies, adverse reactions led to discontinuation of treatment in 8% of placebo patients compared with 6% of TOPAMAX®-treated patients. Adverse reactions associated with discontinuing therapy that occurred in more than one TOPAMAX®-treated patient were fatigue (1%), headache (1%), and somnolence (1%).

Increased Risk For Bleeding

TOPAMAX® is associated with an increased risk for bleeding. In a pooled analysis of placebo-controlled studies of approved and unapproved indications, bleeding was more frequently reported as an adverse reaction for TOPAMAX® than for placebo (4.5% versus 3.0% in adult patients, and 4.4% versus 2.3% in pediatric patients). In this analysis, the incidence of serious bleeding events for TOPAMAX® and placebo was 0.3% versus 0.2% for adult patients, and 0.4% versus 0% for pediatric patients.

Adverse bleeding reactions reported with TOPAMAX® ranged from mild epistaxis, ecchymosis, and increased menstrual bleeding to life-threatening hemorrhages. In patients with serious bleeding events, conditions that increased the risk for bleeding were often present, or patients were often taking drugs that cause thrombocytopenia (other antiepileptic drugs) or affect platelet function or coagulation (e.g., aspirin, nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, or warfarin or other anticoagulants).

Other Adverse Reactions Observed During Clinical Trials

Other adverse reactions seen during clinical trials were: abnormal coordination, eosinophilia, gingival bleeding, hematuria, hypotension, myalgia, myopia, postural hypotension, scotoma, suicide attempt, syncope, and visual field defect.

Laboratory Test Abnormalities

Adult Patients

In addition to changes in serum bicarbonate (i.e., metabolic acidosis), sodium chloride and ammonia, TOPAMAX® was associated with changes in several clinical laboratory analytes in randomized, double-blind, placebo-controlled studies . Controlled trials of adjunctive TOPAMAX® treatment of adults for partial onset seizures showed an increased incidence of markedly decreased serum phosphorus (6% TOPAMAX® versus 2% placebo), markedly increased serum alkaline phosphatase (3% TOPAMAX® versus 1% placebo), and decreased serum potassium (0.4 % TOPAMAX® versus 0.1 % placebo).

Pediatric Patients

In pediatric patients (1-24 months) receiving adjunctive TOPAMAX® for partial onset seizures, there was an increased incidence for an increased result (relative to normal analyte reference range) associated with TOPAMAX® (vs placebo) for the following clinical laboratory analytes: creatinine, BUN, alkaline phosphatase, and total protein, The incidence was also increased for a decreased result for bicarbonate (i.e., metabolic acidosis), and potassium with TOPAMAX® (vs placebo) . TOPAMAX® is not indicated for partial onset seizures in pediatric patients less than 2 years of age.

In pediatric patients (ranging from 6-17 years old) receiving TOPAMAX® for migraine prophylaxis, there was an increased incidence for an increased result (relative to normal analyte reference range) associated with TOPAMAX® (vs placebo) for the following clinical laboratory analytes: creatinine, BUN, uric acid, chloride, ammonia, alkaline phosphatase, total protein, platelets, and eosinophils, The incidence was also increased for a decreased result for phosphorus, bicarbonate, total white blood count, and neutrophils . TOPAMAX® is not indicated for prophylaxis of migraine headache in pediatric patients less than 12 years of age.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of TOPAMAX®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole-General Disorders: oligohydrosis and hyperthermia , hyperammonemia, hyperammonemic encephalopathy , hypothermia with concomitant valproic acid

Gastrointestinal System Disorders: hepatic failure (including fatalities), hepatitis, pancreatitis

Skin and Appendage Disorders: bullous skin reactions (including erythema multiforme, Stevens- Johnson syndrome, toxic epidermal necrolysis), pemphigus

Urinary System Disorders: kidney stones

Vision Disorders: acute myopia, secondary angle closure glaucoma , maculopathy

Hematological Disorders: decrease of the International Normalized Ratio (INR) or prothrombin time when given concomitantly with vitamin K antagonist anticoagulant medications such as warfarin.

Read the entire FDA prescribing information for Topamax (Topiramate)

Topamax Side Effects

Generic Name: topiramate

Medically reviewed by Last updated on Dec 16, 2018.

  • Overview
  • Side Effects
  • Dosage
  • Professional
  • Tips
  • Interactions
  • More

Note: This document contains side effect information about topiramate. Some of the dosage forms listed on this page may not apply to the brand name Topamax.

In Summary

Common side effects of Topamax include: anxiety, ataxia, confusion, diarrhea, diplopia, dizziness, drowsiness, dysphasia, fatigue, lack of concentration, memory impairment, nausea, nervousness, paresthesia, psychomotor disturbance, speech disturbance, depression, visual disturbance, weight loss, dysgeusia, mood changes, and anorexia. Other side effects include: arthralgia, and asthenia. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to topiramate: oral capsule, oral capsule extended release, oral tablet

Along with its needed effects, topiramate (the active ingredient contained in Topamax) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking topiramate:

More common

  • Any vision problems, especially blurred vision, double vision, eye pain, or rapidly decreasing vision
  • burning, prickling, or tingling sensations
  • clumsiness or unsteadiness
  • confusion
  • continuous, uncontrolled back-and-forth or rolling eye movements
  • dizziness
  • drowsiness
  • eye redness
  • generalized slowing of mental and physical activity
  • increased eye pressure
  • memory problems
  • menstrual changes
  • menstrual pain
  • nervousness
  • speech or language problems
  • trouble in concentrating or paying attention
  • unusual tiredness or weakness

Less common

  • Abdominal or stomach pain
  • fever, chills, or sore throat
  • lessening of sensations or perception
  • loss of appetite
  • mood or mental changes, including aggression, agitation, apathy, irritability, and mental depression
  • red, irritated, or bleeding gums
  • weight loss


  • Blood in the urine
  • decrease in sexual performance or desire
  • difficult or painful urination
  • frequent urination
  • hearing loss
  • loss of bladder control
  • lower back or side pain
  • nosebleeds
  • pale skin
  • red or irritated eyes
  • ringing or buzzing in the ears
  • skin rash or itching
  • swelling
  • trouble breathing

Incidence not known

  • Blistering, peeling, or loosening of the skin
  • blisters in the mouth
  • blisters on the trunk, scalp, or other areas
  • bloating
  • clay-colored stools
  • constipation
  • cough
  • diarrhea
  • increased rate of breathing
  • joint or muscle pain
  • pain or tenderness in upper abdomen or stomach
  • red skin lesions, often with a purple center
  • sores, ulcers, or white spots in the mouth or on the lips
  • yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking topiramate:

Symptoms of overdose

  • Decreased awareness or responsiveness
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • severe sleepiness
  • unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

Some side effects of topiramate may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Breast pain in women
  • tremors

Less common

  • Back pain
  • chest pain
  • constipation
  • heartburn
  • hot flushes
  • increased sweating
  • leg pain

For Healthcare Professionals

Applies to topiramate: oral capsule, oral capsule extended release, oral tablet


Rare (less than 0.1%): Raynaud’s phenomenon


Common (1% to 10%): Alopecia, rash, pruritus

Rare (less than 0.1%): Stevens-Johnson syndrome, erythema multiforme, skin odor abnormal, periorbital edema, urticaria localized

Frequency not reported: Toxic epidermal necrolysis, oligohidrosis

Postmarketing reports: Bullous skin reactions, pemphigus


Very common (10% or more): Nausea, diarrhea

Uncommon (0.1% to 1%): Pancreatitis, flatulence, gastroesophageal reflux disease, abdominal pain lower, hypoesthesia oral, gingival bleeding, abdominal distension, epigastric discomfort, abdominal tenderness, salivary hypersecretion, oral pain, breath odor, glossodynia


Uncommon (0.1% to 1%): Erectile dysfunction, sexual dysfunction, renal calculus, intermenstrual bleeding, leucorrhoea, menorrhagia, vaginitis, amenorrhea, urinary tract infections, micturition frequency, urinary incontinence, dysuria

Postmarketing reports: Kidney stones, nephrocalcinosis


Common (1% to 10%): Anemia, epistaxis

Uncommon (0.1% to 1%): Leucopenia, thrombocytopenia lymphadenopathy, white blood cell count decreased, eosinophilia

Rare (less than 0.1%): Neutropenia


Rare (less than 0.1%): Hepatitis, hepatic failure, increase in liver enzymes

Postmarketing reports: Hepatic failure including fatalities


Common (1% to 10%): Hypersensitivity

Frequency not reported: Allergic edema, conjunctival edema


Very common (10% or more): Nasopharyngitis

Frequency not reported: Genital moniliasis


Very common (10% or more): Weight decreased

Common (1% to 10%): Anorexia, decreased appetite, weight increased

Uncommon (0.1% to 1%): Metabolic acidosis, hypokalemia, increased appetite, polydipsia

Rare (less than 0.1%): Acidosis hyperchloremic, blood bicarbonate decreased

Postmarketing reports: Hyperammonemia with and without encephalopathy

Metabolic Acidosis:

Generally, topiramate-induced metabolic acidosis occurs early in treatment; however, it can occur any time. Average decreases of serum bicarbonate of 4 mEq/L have been observed in adults receiving 400 mg/day and pediatrics receiving approximately 6 mg/kg/day. Values below 10 mEq/L have been rarely reported. In adult trials for adjunctive treatment of epilepsy, persistent serum bicarbonate decreases to less than 20 meq/L were reported in 32% of patients receiving 400 mg/day versus 1% of placebo-treated patients. In pediatric trials, adjunctive therapy yielded persistent decreases in serum bicarbonate of 67% for doses of approximately 6 mg/kg/day and 10% for placebo. In monotherapy trials for patients 6 to 15 years, the incidence of persistent decreases in serum bicarbonate was 9% for 50 mg per day and 25% for 400 mg per day. In adult migraine trials, persistent decreases in serum bicarbonate occurred in 44%, 39%, 23%, and 7% of patients receiving 200 mg/day, 100 mg/day, 50 mg/day, and placebo, respectively. In adolescent migraine trials, this was 77%, 27%, 30%, and 9% for those receiving 200 mg/day, 100 mg/day, 50 mg/day, and placebo, respectively.


The incidence of hyperammonemia (above the upper limit of normal) for adolescent patients receiving this drug for migraine prophylaxis was 26%, 14%, and 9% for doses of 100 mg, 50, mg, or placebo, respectively. Hyperammonemia with and without encephalopathy has been reported in the post-marketing period. Hyperammonemia appears to be more common when used concomitantly with valproic acid.


Common (1% to 10%): Arthralgia, muscle spasms, myalgia, muscle twitching, muscular weakness, musculoskeletal chest pain

Uncommon (0.1% to 1%): Joint swelling, musculoskeletal stiffness, flank pain, muscle fatigue

Rare (less than 0.1%): Limb discomfort

Nervous system

Very common (10% or more): Paraesthesia, somnolence, dizziness

Common (1% to 10%): Disturbance in attention, memory impairment, amnesia, cognitive disorder, mental impairment, psychomotor skills impaired, convulsion, coordination abnormal, tremor, lethargy, hypethesia, nystagmus, dysgeusia, balance disorder, dysarthria, intention tremor, sedation

Uncommon (0.1% to 1%): Depressed level of consciousness, grand mal convulsion, visual field defect, complex partial seizures, speech disorder, psychomotor hyperactivity, syncope, sensory disturbance, drooling, hypersomnia, aphasia, repetitive speech, hypokinesia, dyskinesia, dizziness postural, poor quality sleep, burning sensation, sensory loss, parosmia, cerebellar syndrome, dysesthesia, hypogeusia, stupor, clumsiness, aura, ageusia, dysgraphia, dysphasia, neuropathy peripheral, presyncope, dystonia, formication

Most CNS adverse reactions can be classified into 3 categories: cognitive-related dysfunction (e.g. confusion psychomotor slowing, difficulty with concentration/attention, difficulty with memory, speech, or language problems, particularly word-finding difficulties); psychiatric/behavioral disturbances (e.g. depression or mood problems); and somnolence or fatigue. Most were mild to moderate in severity and frequently occurred in isolation. Rapid titration rate and higher initial dose was associated with a higher occurrence.


Common (1% to 10%): Vision blurred, diplopia, visual disturbance

Rare (less than 0.1%): Blindness unilateral, blindness transient, glaucoma, accommodation disorder, altered visual depth perception, scintillating scotoma, eyelid edema, night blindness, amblyopia

Frequency not reported: Angle closure glaucoma, maculopathy, eye movement disorder


Very common (10% or more): Fatigue

Common (1% to 10%): Vertigo, tinnitus, ear pain pyrexia, asthenia, irritability, gait disturbance, feeling abnormal, malaise

Uncommon (0.1% to 1%): Deafness, deafness unilateral, deafness neurosensory, ear discomfort, hearing impaired, hyperthermia, thirst, influenza like illness, sluggishness, peripheral coldness, feeling drunk, feeling jittery, tandem gait test abnormal

Rare (less than 0.1%): Face edema, calcinosis, learning disability

Frequency not reported: Hypothermia, hyperthermia (associated with oligohidrosis)


Very common (10% or more): Somnolence (15%), memory loss (10%), depression

Common (1% to 10%): Depression, difficulty with concentration/attention, anxiety psychomotor slowing, altered mood, confusion, cognitive difficulty, bradyphrenia, decreased libido, expressive language disorder, disorientation, aggression, aggression, anger, abnormal behavior

Uncommon (0.1% to 1%): Suicidal ideation, suicide attempt, hallucination, psychotic disorder, hallucination auditory, hallucination visual, apathy, lack of spontaneous speech, sleep disorder, affect lability, restlessness, crying, dysphemia, euphoria, paranoia, perseveration, panic attack, tearfulness, reading disorder, flat affect, thinking abnormal, listlessness, middle insomnia, distractibility, early morning awakening, panic reaction, elevated mood

Rare (less than 0.1%): Mania, panic disorder, feelings of despair, hypomania

Antiepileptic drugs increased the risk of suicidal thoughts or behaviors when taken for any indication. Pooled analyses of 199 placebo-controlled clinical trials of 11 different antiepileptic drugs showed patients on antiepileptics had approximately twice the risk compared to placebo. In these trials (median duration 12 weeks; most less than 24 weeks), the estimated incidence rate of suicidal behavior or ideation was 0.43% compared to 0.24% which represents an increase of approximately 1 case for every 530 patients treated.


Common (1% to 10%): Nephrolithiasis, pollakiuria, dysuria

Rare (less than 0.1%): Calculus ureteric, renal tubular acidosis

In clinical trials, 1.5% of adult patients receiving this drug developed kidney stones (approximately 2 to 4 times more than expected). The incidence was higher in men. Kidney stone have been reported in pediatric patients taking this drug for epilepsy or migraine.


Common (1% to 10%): Bronchitis, rhinitis, dyspnea, epistaxis, nasal congestion, rhinorrhea, cough

Uncommon (0.1% to 1%): Dyspnea exertional, paranasal sinus hypersecretion, dysphonia

1. “Product Information. Topiramate (topiramate).” Cipla USA Inc., Miami, FL.

2. “Product Information. Qudexy XR Sprinkle (topiramate).” Upsher-Smith Laboratories Inc, Minneapolis, MN.

3. “Product Information. Trokendi XR (topiramate).” Supernus Pharmaceuticals Inc, Rockville, MD.

4. Cerner Multum, Inc. “UK Summary of Product Characteristics.” O 0

5. Cerner Multum, Inc. “Australian Product Information.” O 0

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

Medical Disclaimer

More about Topamax (topiramate)

  • During Pregnancy or Breastfeeding
  • Dosage Information
  • Patient Tips
  • Drug Images
  • Drug Interactions
  • Compare Alternatives
  • Support Group
  • Pricing & Coupons
  • En Español
  • 486 Reviews
  • Generic Availability
  • Drug class: carbonic anhydrase inhibitor anticonvulsants
  • FDA Alerts (6)

Consumer resources

  • Topamax
  • Topamax (Topiramate Sprinkle Capsules)
  • Topamax (Topiramate Tablets)
  • Topamax (Advanced Reading)

Other brands: Trokendi XR, Qudexy XR, Topiragen

Professional resources

  • Topamax (AHFS Monograph)
  • … +1 more

Other Formulations

  • Topamax Sprinkle

Related treatment guides

  • Fibromyalgia
  • Diabetic Peripheral Neuropathy
  • Bulimia
  • Epilepsy
  • … +9 more

Can Topamax help with weight loss?

  • 05 January 2019
  • by: Adam
  • in: Blog
  • This article was written by a Medical Doctor (MD) and reviewed by the thyroid health experts at ThyroMate.

    ThyroMate articles uses only proven, accurate, credible sources (such as research studies and academic papers and websites) in order to provide accurate, fact-checked information about thyroid health that is helpful and objective. All references are linked throughout the article and sources for each are cited at the end. Visit these links to learn more about the research studies and conclusions drawn from the research methods.

    Information contained on this website is not a substitute for medical advice, diagnosis, or treatment. You should always consult your physician for questions related to your health.

    Medically Reviewed

As an increasing number of people is overweight or obese pharmaceutical companies formulate drugs that are meant to kick-start the weight loss process. Some drugs are available with doctor’s prescription only while others are sold in over-the-counter form.

Topamax is a frequently used drug for weight loss, but there is still a lot we need to learn about it. Who can use this drug? Is it effective? Are there any side effects to keep in mind?

You’ll get answers to these and other questions you may have in the post below.

What is Topamax?

First, we’re going to learn a thing or two about the drug. Topamax is a brand name for topiramate, a broad-spectrum anticonvulsant or anti-epilepsy drug. The drug is prescribed for the treatment of seizures in adults and children who are at least two years old. Another use of Topamax is to decrease the frequency of migraines in persons ages 12 and up.

Despite the fact that the underlying mechanism of action is poorly elucidated what we do know is that Topamax works by altering the production or action of neurotransmitters in the brain, thus suppressing the abnormal activity of the nerves in the brain that induce seizures. Additionally, it prevents the abnormal activity of the nerves from spreading to other nerves.

It’s important to mention that Topamax was approved by the FDA in 1996 to treat seizures. The FDA approval for prevention of migraines came in 2004. In 2012, FDA approved the use of Topamax in combination with Phentermine for weight loss.

Even before the official FDA approval, this drug was used off-label for this purpose, so the agency wanted to regulate this field more effectively in order to promote safe use and avoid complications.

Is Topamax effective for weight loss?

Even though the drug was specifically formulated to treat seizures and prevent migraines, it’s also used for weight loss purposes. You probably know someone who’s using Topamax for weight loss, or maybe you were considering asking doctor for a prescription. Regardless of the scenario chances are high you’re wondering whether Topamax really works. Current evidence is very promising.

For example, Kramer et al. published a study in Obesity Reviews which found that topiramate can, indeed, promote weight loss. Scientists summarized evidence on the safety and efficacy of topiramate in the treatment of overweight and obesity. They searched for evidence in different databases. In order to be eligible for the review studies needed to last at least 16 weeks. Ten studies were identified, and they had 3320 subjects in total.

Findings revealed that participants who took topiramate lost an average of 5.34kg of additional weight compared to placebo. Efficacy of the topiramate depended on dosage and duration of the treatment. For instance, 96-200mg topiramate a day resulted in higher weight loss in trials that lasted 28 weeks or more than in studies that were shorter in duration. Researchers concluded the study explaining that topiramate might be a useful therapeutic weight loss tool as long as side effects are considered.

Moradi et al. carried out a study to assess the effects of topiramate on weight loss in subjects with type 2 diabetes. The 32-week randomized clinical trial included 69 subjects which received either topiramate or placebo. Results, published in the Journal of Research in Medical Sciences, found that BMI changes were significantly higher in subjects who took topiramate. The drug-induced weight loss and improved glycemic control in participants.

Scientists explained that treatment of obese diabetic patients with 150mg/day topiramate can be suitable for near 5% weight loss and the drug may be effective in improving metabolic parameters associated with obesity and glycemic control in patients with type 2 diabetes.

Phentermine and topiramate for weight loss

As seen above, studies do support the weight loss effects of Topamax. Pieces of evidence displayed above focused on the use of Topamax itself, but topiramate is also used in combination with phentermine. Gadde et al. carried out a study which “assessed the efficacy and safety of two doses of phentermine plus topiramate combination as an adjunct to diet and lifestyle modification for weight loss.”

It’s useful to mention that phentermine is one of the most frequently prescribed weight loss drugs. The 56-week trial enrolled 2487 participants ages 18 to 70. Subjects were assigned either to phentermine/topiramate combination or placebo group. The popular journal Lancet published results which found that a combination of two drugs provides its benefits even at lower doses. This led to the conclusion that phentermine and topiramate combined might be a valuable treatment for obesity.

Not only does Topamax work for weight loss on its own, but it’s also effective when used in combination with phentermine. Besides the above-mentioned study, Garvey et al. conducted their own research which lasted for 52 weeks and enrolled 676 subjects.

Some participants received a combination of phentermine and topiramate while others took a placebo. Results, featured in the American Journal of Clinical Nutrition, revealed that a combination of phentermine and topiramate in conjunction with lifestyle modifications might provide an effective and well-tolerated treatment of obesity complicated by cardiometabolic disease.

What makes this study so important is that it confirmed weight loss potential of phentermine and topiramate combination, but also showed that effects are well-maintained. This means the drug can help patients avoid the unpleasant and frustrating yo-yo effect which occurs when people gain more weight after treatment than they lost during.

As you can see, a growing body of evidence confirms that topiramate, when used in combination with phentermine, can contribute to sustained weight loss. Topiramate is a generic form of the drug that is sold under brand name Topamax which can help users slim down on its own, as mentioned throughout this post.

How does Topamax work for weight loss?

Despite the fact that some studies found Topamax effective for treatment of weight loss it’s crucial to mention the drug is still not researched enough. Current evidence, while promising, does not inspect long-term effects of the drug. At the same time, there is no specific dosage that proves to be the most effective for weight loss purposes as studies focused on different doses. A lot of uncertainties are involved, and the only way to resolve them is to carry out further research on Topamax for weight loss.

While topiramate in combination with phentermine is FDA-approved for weight loss, Topamax on its own is not. So, using this drug to slim down means you’re going off-label. As mentioned above, Topamax has FDA approval for seizures and migraines. The mechanism of action through which Topamax contributes to weight loss is unknown. Various theories are involved including:

  • Loss of taste sensation – Topamax use changes taste sensation due to a reduction of saliva. Some patients lose the sense of pleasure associated with food because they don’t like how it tastes anymore. As a result, they eat less which leads to weight loss and weight management. A big problem nowadays is that we tend to eat more than our body needs to function optimally. Overeating leads to weight gain and other problems
  • Decreased production of cortisol – stress hormone cortisol increases blood glucose production, and it can also increase your appetite and cravings. Through decreased concentration of cortisol, Topamax promotes anti-stress effects, improve psychological well-being, but also allows users to avoid overeating. By lowering cortisol, the drug also decreases leptin (hunger home) present in cortisol meaning you’re not hungry as often as you used to be
  • Acts on addiction centers in the brain – Topamax alters neurotransmitters in your brain which is why it can decrease the frequency and severity of seizures and migraines. The same way, it can also promote weight loss. Some people seek solace and comfort in food, they develop addictive behavior, and the result is an excessive weight gain. By acting on addiction centers in the brain, Topamax may make a person less interested in engaging in that behavior which can lead to lower calorie intake and ensuing weight loss.

Bear in mind that underlying mechanisms through which Topamax works are still not fully elaborated. At this point, it’s not clear how the drug acts with long-term use.

Therefore, before you ask the doctor for a prescription for this drug you need to take various factors in consideration including the fact this is not a quick fix. It’s not uncommon for people to start taking a weight loss drug and expect it to do wonders quickly without lifestyle modifications.

Even if your doctor prescribes Topamax or a combination of topiramate and phentermine for weight loss, you need to bear in mind results won’t occur overnight. Patience is vital just like necessary lifestyle modifications such as regular exercise and a well-balanced diet.

Topamax side effects

Kramer’s study showed that Topamax could be effective for weight loss if side effects are considered. In fact, a major reason why some doctors don’t prescribe this drug to their patients is the risk of potentially serious side effects. Adverse reactions associated with the use of Topamax include, but are not limited to:

  • Depression, anxiety, nervousness and other mood changes
  • Dizziness
  • Double vision and other vision changes
  • Fatigue
  • Fever
  • Hair loss
  • Insomnia
  • Slowed thinking
  • Tremors
  • Weakness

Potentially serious side effects of Topamax include:

  • Bleeding gums
  • Blood cell count changes
  • Bone density changes
  • Elevated body temperature
  • Glaucoma, acute myopia, or maculopathy and other vision problems
  • Kidney stones
  • Low potassium levels
  • Memory problems
  • Pale skin
  • Psychosis or suicidal tendencies
  • Speech and language problems
  • Stomach pain

Some studies showed that Topamax was well-tolerated while others found the drug did induce some serious side effects. Of course, this doesn’t mean you’d experience adverse reactions for sure, but it’s useful to consult a healthcare provider and take side effects of Topamax into consideration before using the drug.

Interactions with other drugs

Topamax may interact with an anti-obesity drug called orlistat. In addition, the drug may reduce the effectiveness of hormonal birth control products.

Topamax may also interact with drugs for sleep and anxiety, antihistamines, muscle relaxants, and narcotic pain relievers. Make sure you inform the doctor about all prescription and over-the-counter medications or supplements you use to decrease the risk of interactions. Your doctor will inform you whether Topamax could interact with other medications you’re taking.


No specific dosage of Topamax for weight loss has been determined so far which only shows why more research is needed on this drug. In most cases, patients start with lower doses of 25mg to 50mg a day and increase it by 25-50mg a week until an effective dosage is reached. Of course, all this is performed with doctor’s supervision and guidance. Patients should never increase or decrease dosage on their own.

Who should avoid Topamax?

You need to avoid Topamax if you’re pregnant or breastfeeding. People with a history of depression and suicidal thoughts or tendencies also need to exercise caution when it comes to Topamax. You may want to avoid the drug if you have low potassium levels in the blood too. Topamax may also not be suitable for persons with epilepsy who are treated with a keto diet.


Topamax is a drug formulated to treat seizures, but it’s also used for migraines.

Studies show it may be effective for weight loss on its own and when topiramate is used in combination with phentermine. It may exhibit serious side effects so you need to consult your doctor before deciding whether you should use Topamax or some other pill for weight loss. Remember, the pill is not a replacement for a healthy diet and regular exercise.

Is Half-Life a Clinically Relevant Measure for Extended-Release Drugs? Data Comparing Immediate- and Extended-Release Topiramate (USL255; Qudexy™ XR) (P1.249)


Objective: Describe different half-life measures and compare immediate- and extended-release topiramate (TPM-IR and USL255 ) Background: Clinicians frequently use elimination half-life (t1/2z; time to decrease drug concentration by half after absorption and redistribution) to determine dosing frequency and time to steady state. However, t1/2z may not always be appropriate because XR formulations can exhibit prolonged absorption, and most drugs, including topiramate, redistribute into multiple tissue compartments. A more appropriate parameter to predict multidose drug accumulation may be effective half-life (t1/2eff), rate of drug loss over a dosing interval. Design/Methods: Half-lives were compared using data from a phase 1, randomized (N=36), open-label, single-dose crossover study of 200mg USL255 QD and 100mg TPM-IR BID. Plasma concentrations were measured for 336h using an assay with 10ng/mL lower limit of quantification. Pharmacokinetic parameters included t1/2z, t1/2eff, and time to maximum plasma concentration (Tmax). t1/2z was calculated using the terminal phase slope whereas t1/2eff accounted for dosing interval and accumulation index. Results: t1/2z was similar for USL255 (80h) and TPM-IR (83h); however, t1/2eff was markedly different (56 vs 37h). USL255 Tmax was longer than TPM-IR, indicating slower absorption. TPM-IR t1/2z observed here is longer than reported in the Topamax product information (83 vs 21h), likely due to longer sampling time and increased assay sensitivity. Conclusions: Despite differences in recommended dosing, t1/2z of USL255 and TPM-IR were similar, which may lead to the assumption that changes in plasma concentration over 24h are similar. In contrast, USL255 displayed a longer t1/2eff versus TPM-IR, predictable for a measure that takes into account absorption. This difference in t1/2eff better reflects the once- vs twice-daily dosing that is recommended for USL255 and TPM-IR. Though half-life is a commonly recognized drug-elimination parameter, t1/2eff may be more clinically relevant for XR drugs. Study Supported by: Upsher-Smith Laboratories, Inc.

Disclosure: Dr. Gidal has received personal compensation for activities with GlaxoSmithKline, UCB Pharma, Eisai, Sunovian, and Upsher Smith Laboratories, Inc. as a consultant and/or speaker. Dr. Gidal has received research support from GlaxoSmithKline and UCB Pharma. Dr. Clark has received personal compensation for activities with Upsher-Smith Laboratories, Inc. as an employee. Dr. Anders has received personal compensation for activities with Upsher-Smith Laboratories, Inc. as an employee.

Topamax/Topiramate Treatment

Home Topamax/Topiramate Treatment

According to Medical News Today, alcoholism and addiction are the fifth most common diseases in the world and the third most common diseases in the United States. In an effort to reduce these rates, medical researchers continue to look for ways to reduce or eliminate alcoholism and drug addiction problems.

Topamax (the brand name) and topiramate (its generic counterpart) produce certain key nervous system effects. Because of this, these drugs are currently being studied to better understand how they afffect alcoholism and drug addiction processes. Like most other medications, Topamax and topiramate have benefits and drawbacks that can vary depending on a person’s current health status. If you suffer from an addiction problem, you may want to look into ongoing developments involving Topamax and topiramate drug studies.

Treatment Using Topamax or Topirmate

Both Topamax and generic topiramate are prescription drugs commonly used to treat individuals who suffer from seizure disorders. They are also used to reduce or prevent migraine headaches in adults. As of yet, Topamax is not federally approved as a treatment for alcoholism or addicition, though current research studies do hold promise in terms of its effectiveness as a treatment. Topamax comes in tablet and capsule forms with dosages ranging from 15 to 200 milligrams.

If you read one thing about executive or luxury addiction treatment, read this.

Once ingested, Topamax effects can last anywhere from 19 to 23 hours based on its half-life duration. Because of the chemical makeup of the drug, 50 to 80 percent of it is excreted through the urine in an unchanged form. This means no blood level monitoring tests are necessary as Topamax does not accumulate in the bloodstream. This drug does interact with several types of medications, so if you’re considering undergoing a Topamax drug trial, be sure to list any and all medications you’re currently taking.

Because of its effects on alcoholism and addiction, Topamax is also being considered as a treatment for nicotine and cocaine dependencies. Other research studies currently underway are examining Topamax’s effectiveness in treating mood disorders, essential tremors, diabetes and nerve pain disorders. Coincidently, each these conditions can also develop after years of alcohol use.

*The Effects of Topamax on Drinking Behaviors

The combined results from ongoing Topamax studies identify key areas where the drug can benefit people who suffer from alcoholism. Study participants reported improvement in the following key areas:

  • They experienced fewer days of heavy drinking.
  • They experienced more days where no alcohol was consumed at all.
  • They consumed fewer drinks per day.
  • Some who consumed fewer drinks per day were reclassified as “moderate” drinkers as opposed to “heavy” drinkers.

Treatment for Alcoholism

Alcohol dependency develops over time as the effects of ongoing alcohol use start to alter the brain’s normal chemical processes. Brain chemicals – also known as neurotransmitters – regulate different processes in the brain that affect emotions, reasoning abilities and motor functions. After years of ongoing alcohol use, the brain’s chemistry becomes dependent on alcohol’s effects. When this happens, the brain is unable to secrete normal levels of neurotransmitter chemicals. Glutamate, dopamine and GABA (gamma-aminobutyric acid) are the neurotransmitter chemicals most affected by ongoing alcohol use.

After years of drinking, the brain secretes low levels of GABA and higher than normal levels of glutamate. Research trials conducted by the University of Texas in San Antonio show Topamax effects help to alter the brain’s neurotransmitter levels by increasing the amount of GABA secreted while decreasing dopamine and glutamate secretions.

Over time, Topamax’s effects on brain neurotransmiter levels resulted in a decrease in the number of heavy drinking days for those who participated in the research trial. Participants also craved alcohol less, which resulted in an increase in the number of days they were able to go without drinking.

*FDA-Approved Medication Treatments for Alcohol and Drug Dependence

FDA-approved treatments for alcoholism and drug addiction can vary considerably in terms of the benefits they provide. Some of the drugs currently in use include:

  • Opioids/ methadone, naltrexone and buprenorphine: Used in the treatment of opiate addictions
  • Acomprosate: Used to treat alcohol withdrawal symptoms
  • Disulfiram: Used as a negative reinforcement treatment for alcoholism
  • Naltrexone: Used to reduce alcohol cravings

Treatment for Drug Addiction

Brain neurotransmitters (or chemicals) can either stimulate or slow brain activity. Those that stimulate brain activity are known as excitatory neurotransmitters, while those that slow activity are known as inhibitory transmitters. GABA secretions function as inhibitory neurotransmitters while dopamine and glutamate have excitatory effects. Much like alcoholism, ongoing drug use increases glutamate levels in the brain and decreases dopamine and GABA levels. Over time, GABA secretions become depleted when high levels of glutamate levels are present.

Research studies conducted by the University of Pennsylvania examined the effects of Topamax on trial participants who suffered from cocaine dependency. Ongoing cocaine use tends to increase glutamate levels in the brain and decrease GABA levels. The effects of Topamax or topiramate helped to restore brain chemical levels to normal by decreasing the amount of glutatmate secreted and increasing the amount of GABA secretions. After eight weeks, trial participants were able to abstain from cocaine usage with some participants able to go as long as three weeks without using.

Adverse Effects

Since Topamax and topiramate are currently used to treat seizure and migraine conditions, information regarding any adverse effects from using the drug are fairly well known. It’s used as an anti-convulsant or anti-seizure medication because of its effects on the body’s nerves or nervous system. So, anyone who takes Topamax or topiramate for alcoholism or addiction treatment may experience occassional numbess or tingling in the arm, hands, legs and feet.

Adverse effects may also take the form of impaired memory and concentration as Topamax does have a direct effect on the brain’s overall chemical process. The research trial conducted by the University of Texas showed participants also developed unusually high rates of kidney stones compared to rates found among the general public. Weight loss was another side effect from using the drug, which makes Topamax a candidate for future research studies on weight loss treatments.

Other possible adverse effects from Topamax or topiramate include:

  • Mood swings
  • Problems with coordination
  • Headaches
  • Constipation
  • Pain in the back, muscles or bones

*Clinical Drug Trials

The U.S. National Institutes of Health Administration carries out ongoing clinical drug trials as part of their medical research program. Anyone interested in participating in a Topamax or topiramate trial can find information at the Clinical Trials website.

Clinical drug trials may involve answering health questionnaires, taking experimental treatments or participating in projects that use existing treatments in new ways.


If you’re struggling with alcoholism or drug addiction, you may want to take certain precautions before participating in a Topamax drug trial as the drug tends to interact with a wide range of medications and physical conditions. Whether you’re taking prescription or nonprescription drugs, such as vitamins or nutritional supplements, Topamax’s effects on brain chemistry can affect how the body reacts to other drugs.

Some of the medications known to interact with Topamax and topiramate include:

  • Hormonal contraceptives
  • Anxiety medications
  • Lithium
  • Iron
  • Pain relievers
  • Sedatives

People with existing medical conditions may also experience unexpected effects when taking Topamax or topiramate. Any condition that affects the respiratory system, such as asthma or COPD, may worsen after taking the drug. Anyone with a type of bone disorder, such as osteoporosis or osteopenia, may also experience problems. Diabetes conditions can also be affected. As any neurotransmitter changes in the brain have the potential to alter the body’s hormonal systems, any contraceptive medications may become ineffective when taking Topamax or topiramate.

Topamax is also known for its ability to prevent the body from secreting sweat, which is the body’s way of regulating heat and temperature levels. This means anyone taking Topamax should drink lots of fluids and avoid prolonged exposures to heat.

It’s not uncommon for people suffering from alcohol or drug addictions to have other mental or psychological conditions, such as depression, bipolar disorder or anxiety-related conditions. As Topamax and topiramate affect the brain centers that regulate moods and emotions, anyone suffering from one of these conditions or anyone taking medication to treat a psychological condition should consult with their doctor before trying these drugs. This goes for any medications or conditions you may have.

If you suffer from addiction currently, it’s important to get into a treatment program as soon as possible. An ideal program will combine the use of medications with effective addiction counseling and complementary therapies. Contact us today for help finding such a program.


Before taking topiramate,

  • tell your doctor and pharmacist if you are allergic to topiramate, any other medications, or any of the ingredients in topiramate tablets, sprinkle capsules, and extended-release capsules. Ask your pharmacist for a list of the ingredients.
  • tell your doctor if you have metabolic acidosis (a disturbance in the body’s acid-base balance that results in excessive acidity of the blood) and you are taking metformin (Fortamet, Glucophage, Riomet, others). Your doctor will probably tell you not to take metformin if you have metabolic acidosis and you are taking this of medication.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: acetazolamide (Diamox); amitriptyline; antidepressants; antihistamines; digoxin (Lanoxin); hydrochlorothiazide (Microzide, Oretic); lamotrigine (Lamictal); lithium (Lithobid); medications for motion sickness, ulcers, or urinary problems; metformin (Fortamet, Glucophage, Riomet, others); hormonal contraceptives (birth control pills, patches, rings, implants, or injections); other medications for seizures such as carbamazepine (Epitol, Equetro, Tegretol, Teril), phenytoin (Dilantin, Phenytek), valproic acid (Depakene), and zonisamide (Zonegran); and pioglitazone (Actos, in Actoplus Met ER). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you or any family members have or have ever had kidney stones, and if you have ever thought about killing yourself or tried to do so. Also tell your doctor if you have or have ever had metabolic acidosis (a disturbance in the body’s acid-base balance that results in excessive acidity of the blood); osteopenia, osteomalacia, or osteoporosis (conditions in which the bones are soft or brittle and may break easily); diabetes; glaucoma (a type of eye disease); any disease that affects your breathing such as asthma or chronic obstructive pulmonary disease (COPD); depression or abnormal moods; a growth problem; or liver or kidney disease. Also tell your doctor if you have diarrhea or if you develop diarrhea during your treatment.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you are pregnant or plan to become pregnant, your doctor may prescribe a different medication instead of topiramate because topiramate may harm the fetus. If you do not plan to become pregnant, you should use birth control to prevent pregnancy during your treatment with topiramate. Talk to your doctor about what type of birth control you should use, because taking topiramate may decrease the effectiveness of some types of birth control. If you become pregnant while you are taking topiramate, call your doctor right away, but do not stop taking topiramate before talking to your doctor.
  • if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking topiramate.
  • you should know that topiramate may make you drowsy, dizzy, confused, or unable to concentrate. Do not drive a car or operate machinery until you know how this medication affects you.
  • if you are taking topiramate to control seizures, you should know that you may continue to have seizures during your treatment. You may need to avoid activities such as swimming, driving, and climbing so that you will not harm yourself or others if you lose consciousness during a seizure.
  • tell your doctor if you if you drink alcohol. You should not drink alcohol within 6 hours before and 6 hours after you take extended-release capsules (Trokendi XR brand only). Your doctor will probably tell you not to drink alcohol while taking topiramate.
  • you should know that topiramate can prevent you from sweating and make it harder for your body to cool down when it gets very hot. This happens most often in warm weather and to children who take topiramate. Avoid exposure to heat, drink plenty of fluids and tell your doctor if you have a fever, headache, muscle cramps, or an upset stomach, or if you are not sweating as usual.
  • you should know that you may be more likely to develop a kidney stone while you are taking topiramate. Drink 6 to 8 glasses of water every day to prevent kidney stones from forming.
  • you should know that your mental health may change in unexpected ways and you may become suicidal (thinking about harming or killing yourself or planning or trying to do so) while you are taking topiramate for the treatment of epilepsy, mental illness, or other conditions. A small number of adults and children 5 years of age and older (about 1 in 500 people) who took anticonvulsants such as topiramate to treat various conditions during clinical studies became suicidal during their treatment. Some of these people developed suicidal thoughts and behavior as early as 1 week after they started taking the medication. There is a risk that you may experience changes in your mental health if you take an anticonvulsant medication such as topiramate, but there may also be a risk that you will experience changes in your mental health if your condition is not treated. You and your doctor will decide whether the risks of taking an anticonvulsant medication are greater than the risks of not taking the medication. You, your family, or your caregiver should call your doctor right away if you experience any of the following symptoms: panic attacks; agitation or restlessness; new or worsening irritability, anxiety, or depression; acting on dangerous impulses; difficulty falling or staying asleep; aggressive, angry, or violent behavior; mania (frenzied, abnormally excited mood); talking or thinking about wanting to hurt yourself or end your life; withdrawing from friends and family; preoccupation with death and dying; giving away prized possessions; or any other unusual changes in behavior or mood. Be sure that your family or caregiver knows which symptoms may be serious so they can call the doctor if you are unable to seek treatment on your own.



Nearly 12%-14% of patients on TPM commonly experience transient parasthesia in the face, mouth and extremities early during treatment which disappears spontaneously or with the use of potassium therapy, however, it may be severe and intolerable in some patients and resulted in discontinuation of TPM. Some evidence suggests that the tendency to cause paresthesia is due to TPM effect on an enzyme called carbonic anhydrase which is an enzyme found in nerve tissue, and probably helps nerve cells talking to one another. However, it seems that another cause of parasthesia may occur with chronic TPM therapy due to the effect of TPM on peripheral nerves. This is the first report of presence of peripheral neuropathy in a patient with epilepsy due to chronic therapy with TPM. Peripheral neuropathy induced by TPM is manifested by parathesia in both lower limbs, decreased ankle jerks, stocking distribution of hypesthesia and delayed distal latencies, reduced nerve conduction velocities of motor and sensory peripheral nerves and reduced amplitudes of motor and sensory action potentials of the peripheral nerves of the lower limbs, indicating demyelinating and axonal peripheral neuropathy. As the patient is seizure free on TPM after several years of ineffective other AEDs therapies, I was unable to do re-challenge testing (stopping and re-staring the treatment to be sure that it was the cause peripheral neuropathy). Only reassurance of the patient was done and no specific treatment was prescribed as the patient has mild paraesthesia and non-progressive peripheral neuropathy.

In general, AEDs are used to treat cortical hyperexcitable states which result in epilepsy and peripheral nerve hyperexcitability which both result in neuropathic pain. Regarding TPM, some experimental and clinical studies demonstrated its efficacy to treat neuropathic pain. Lopes et al demonstrated the antinociceptive effect of oral administered doses of TPM (80 mg/kg) in the models of nociception induced by chemical (formalin) or thermal (hot plate) stimuli. Siniscalchi et al reported complete improvement of idiopathic glossodynia in a 65-year-old woman with 4 mo history of glossodynia with TPM after failure of CBZ or GPN. Glossodynia is a painful sensation in the mouth, throat and especially the tongue due to altered excitability in the trigeminal nociceptive pathway at peripheral and/or central nervous system levels. In another study, Siniscalchi et al reported improvement of dysesthetic pain with TPM (150 mg/d within 8 mo) in a 42-year-old woman with 8 years history of multiple sclerosis. Erdoğan et al observed a significant decrease in the strength duration time constant (which provides an indirect idea about the persistent, paranodal sodium channels and may indirectly reflects the peripheral nerve excitability) but did not observe significant affection of median nerve motor and sensory conduction parameters after the initiation of TPM for 4 wk, reflecting a reduction in the peripheral nerve excitability induced by TPM.

In the literature, peripheral neuropathy had been reported as a rare adverse effect with short-term treatment (hours to weeks) with PHT in toxic or non-toxic doses and with long-term (months to years) PHT therapy. Acute peripheral neuropathy induced by PHT is very rare and reversible side effect. Hopf et al reported slight but significant reduction in the mean ulnar nerve conduction velocity in 13 patients after the intake of 500-600 mg PHT per day for a week which was not correlated with serum PHT levels. Lovelace and Horwitz reported decrease in motor and sensory conduction velocities of the peripheral nerves without any symptoms (occult) during PHT administration among patients with epilepsy. Birket-Smith and Krogh reported peripheral neuropathy with PHT level more than 20 μg/mL, however, no correlation was observed between the clinical toxicity severity and the degree of conduction velocity abnormalities. Meienberg et al reported acute severe mainly motor polyneuropathy in the legs and cerebellar symptoms after treatment of a 34-year-old epileptic male with high doses PHT to control status epilepticus although this patient was treated for more than ten years with an average of 300 mg PHT and 200-300 mg phenobarbital (PB) daily. Fujiwara et al reported prolonged distal latency of the tibial nerve and decreased mixed nerve action-potential amplitudes of the posterior tibial and median nerves. Wessely et al reported an axonal polyneuropathy with minimal reduction in motor nerve conduction and a considerable extension of distal latency and diminution of compound action potential in 5 patients who were treated with long-term PHT for epilepsy. In 4 cases, the symptoms appeared following treatment of status epilepticus with additional PHT medication. All patients had acute symptomatic psychosis, diffuse slowing of the curves in the EEG and cerebellar signs and two of them additionally complained of objective polyneuropathy. Nerve biopsy in one patient showed concentric lamellar bodies coming from the axon with intact myelin sheaths. Ramirez et al reported a 47-year-old man with clinical and electrophysiological signs of peripheral neuropathy after 30 years treatment with PHT (300 mg/d, the blood levels were 31-38 μg/mL). A sural nerve biopsy showed loss of large myelinated nerve fibers and non-random clustered distribution of segmental demyelination, remyelination and axonal shrinkage. Clinical and electrophysiological improvement was observed within 16 mo of PHT withdrawal. Yoshikawa et al reported an 18-year-old girl who developed distal lower extremity paresthesia in a stocking distribution, motor weakness, absent Achilles tendon reflexes, slightly reduced sensory conduction velocities and mild prolongation of distal latencies in the lower extremities just few hours after the administration of PHT to control epilepsy. Discontinuation of PHT resulted in gradual disappearance of the symptoms and returning of the distal latencies and sensory conduction velocities to normal. Le Quesne et al demonstrated acute slowing of motor nerve conduction velocity in guinea pigs after only 3-4 d of PHT administration. Furthermore long-term PHT administration can cause of peripheral neuropathy which is more frequent than acute forms. Eisen et al reported peripheral neuropathy with the use of PHT which was correlated with PHT level. Chokroverty and Sayeed reported significant reduction in the mean motor conduction velocity of posterior tibial nerves of epileptic patients treated with PHT for more than 10 years or in patients with serum PHT level above 20 μg/mL. Dobkin reported dysesthesia and sensory and reflex loss in the legs in a patient treated for seizures with PHT in the therapeutic range for one year. Discontinuation of PHT resulted in resolution of peripheral neuropathy. Mochizuki et al reported slowed motor conduction velocities of the ulnar (33.3%) and posterior tibial nerves (23.8%), followed by slowed sensory conduction velocities of the sural nerves (20%), lowered H/M ratio (14.3%), and slowed motor conduction velocities of the peroneal (14.3%) and median (14.2%) nerves in children with epilepsy. The authors observed significant correlations between the total dosage and duration of therapy with PHT and the reduction of motor conduction velocity in the posterior tibial nerve.

Peripheral neuropathy had been also reported with other AEDs therapy as CBZ, PB, VPA, GPN, LEV and LCM. A review of the literature showed that reflex sympathetic dystrophy (RSD) is precipitated by PB in 10%-30% of cases. RSD syndrome is clinically characterized by pain and edema of one or more extremities, trophic skin changes and vasomotor instability. Swift et al reported that 16.7% of epileptic patients may develop peripheral neuropathy with different AEDs which is characterized by stocking hypesthesia, reduced Achilles reflexes, slowing of peroneal and sural nerve conduction velocities and prolonged or absent H reflexes and F responses. Geraldini et al reported slowing of the peroneal and median motor nerve conduction velocities and median sensory nerve conduction velocities with CBZ, PB and PHT. Significant correlation was identified between the slowing of the conduction velocity and the daily dose of CBZ but not its serum drug level or duration of treatment. In the study done by Bono et al on 141 adult patients treated for less than 6 mo with standard daily doses of the commonest AEDs, the authors reported that 53% of patients had one or more symptoms of polyneuropathy (paresthesias being the most common complaint). The neurologic examination was abnormal in 32%. Electrophysiologic findings in two or more separate nerves were abnormal in 77 patients (54.6%); of these, 27 (19.1%) had abnormal neurologic findings and 21 (14.9%) also had symptoms of polyneuropathy. Sensory functions were the most frequently impaired. Axonal damage with secondary myelin changes was noted in sural nerve biopsies of patients on CBZ, PB and PHT. A correlation was noted between polyneuropathy and combined therapy with two or more AEDs. Gould reported a 58-year-old man who developed a painful polyneuropathy while being treated with GPN although GPN is considered an effective treatment for neuropathic pain syndromes. Kapoor et al reported a case of polyneuropathy induced by LEV which improved with discontinuation of LEV. Boylu et al reported mild prolongation in the distal latency of median sensory, ulnar sensory and sural nerves with diminished nerve conduction velocities with chronic CBZ therapy but not with VPA, oxcarbazepine (OXC) or TPM. Marusic et al reported a 26-year-old man with weakness of flexion and abduction of the right arm and loss of sensation in the skin over the lateral upper right arm and reduced amplitude and prolonged latencies in the right axillary nerve because of a suicide attempt with VPA overdose (serum VPA level = 2896 μmol/L; therapeutic range = 350-690 μmol/L). In an experimental study, Zafeiridou et al observed a differential effect for LCM, PHT and TPM on peripheral nerve excitability. The authors reported inhibition of compound action potential of the sciatic nerve of an adult rat after 48 h period of LCM exposure at concentrations higher than the therapeutic level (> 25 μg/mL). An acute and immediate increment of the latency and decrement of the amplitude of the nerve compound action potential were observed at LCM concentrations of 62.57-125.15 μg/mL. However, in contrast to LCM, PHT resulted in an acute decrement in the amplitude of the nerve compound action potential as well as an increment in the latency of the compound action potential even at sub-therapeutic levels (5 μg/mL). Reduced compound motor action potential amplitude was also observed with TPM at concentration of 33.94 μg/mL (supra-therapeutic).

The mechanism (pathogenesis) of PHT induced peripheral neuropathy is not well known. Experimental studies demonstrated a depressant effect of PHT on peripheral nerves which has been attributed to the direct toxic effect of the drug on peripheral nerves and/or due to blockage of sodium channels which is its main anticonvulsant mechanism of action. Korey demonstrated an inhibitory effect of PHT on the giant axon of the squid which was made hyperexcitable by low calcium and magnesium levels. Eisen et al reported a primary axonal shrinkage and secondary demyelination with PHT. Long et al and Hansen et al demonstrated that peripheral neuropathy induced by PHT was related to the subnormal serum folate in association with megaloblastic anemia. We suggest that peripheral neuropathy induced by TPM may be related to its anticonvulsant mechanism of action which is multifactorial and involve blockade of voltage-dependent sodium channels (similar to PHT); inhibition of high-voltage-activated calcium channels; potentiation of GABAergic transmission through GABA-A receptors; inhibition of excitatory pathways through an action at α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) AMPA/kainate receptors sites and inhibition of carbonic anhydrase isoenzymes.

We report a patient with peripheral neuropathy after chronic therapeutic dose of TPM. However, this adverse effect was mild, static and tolerated by the patient and did not disappear with vitamin B supplementations. There is also a need for experimental and clinical studies to identify the effect of TPM on peripheral nerves and to identify the mechanism(s) of TPM induced peripheral neuropathy.

Topiramate for treating neuropathic pain or fibromyalgia

Neuropathic pain is pain coming from damaged nerves. It is different from pain messages carried along healthy nerves from damaged tissue (for example from a fall, a cut, or arthritic knee). Neuropathic pain is treated by different medicines than pain from damaged tissue. Medicines like paracetamol or ibuprofen are not effective in treating neuropathic pain, while medicines that are sometimes used to treat depression or epilepsy can be very effective in some people with neuropathic pain. Our knowledge about fibromyalgia is even less advanced, but fibromyalgia can respond to the same medicines as neuropathic pain.

Topiramate is a medicine used to treat epilepsy, and so it might be a useful medicine for neuropathic pain or fibromyalgia.

On 8 May 2013, we performed searches to look for clinical trials on the use of topiramate to treat neuropathic pain or fibromyalgia. We found four studies of reasonable quality that tested topiramate against placebo for a number of weeks. Almost all of the 1684 people in the studies had painful limbs because of damaged nerves caused by diabetes.

Topiramate did not help the pain and was no different from placebo except in causing more side-effects, which made many more people withdraw from the studies early. About 3 people in 10 withdrew because of side-effects with topiramate compared with 1 in 10 with placebo.

Topiramate has not been shown to work as a pain medicine in diabetic neuropathy.

Neuropathic pain is a chronic nerve pain that can significantly impair a patient’s functioning and quality of life. Neuropathic pain results from damaged nerves that have been affected by tissue injury due to trauma or disease. Diabetes mellitus and herpes zoster are commonly associated with the development of neuropathies. Other disease states that may result in neuropathic pain include complex regional pain syndrome, radiculopathy, and phantom limb pain. Neuropathic pain can also be medicationrelated, as in the case of nerve damage due to cancer treatment.
Neuropathic pain originates from the reduced inability of a neuron to relay messages to and from the brain because of damage to the nerve. This can cause a person to feel a variety of sensations or hypersensitivities.1,2 A patient may feel different types of pain, depending on the origin and cause of the pain.
Neuropathic pain can be distinguished from nociceptive pain by determining the quality of the pain. Typically, patients experience variations in sensation or hypersensitivity. Neuropathic pain symptoms can be classified as negative or positive. Negative symptoms of neuropathic pain are described as a loss of sensation or numbness. Positive symptoms are characterized by the increased perception of pain or abnormal sensations. Positive symptoms can be either induced by a stimulus or spontaneous (nonstimulus induced). Table 1 describes the types of symptoms.
Various classes of medications have shown benefit for managing neuropathic pain. Medications for neuropathic pain are not likely to completely resolve pain; therefore, health care providers should discuss realistic goals with patients prior to initiating therapy. A reduction in pain of 30% is often considered a reasonable goal, along with potential improvements in sleep and depression, depending on the specific agent used. Patients should also be informed that many agents used for neuropathic pain often require a series of dose titrations and weeks of use to see a benefit. Classes of medications used for neuropathic pain include tricyclic antidepressants (TCAs), serotonin/ norepinephrine reuptake inhibitors (SNRIs), anticonvulsants, and, potentially, opioid therapy.3
Tricyclic Antidepressants
TCAs are often considered first-line for treatment of neuropathic pain and have shown benefit in clinical trials for diabetic peripheral neuropathy and postherpetic neuralgia.4 Benefits include low cost, as well as potential improvement in depression and/ or insomnia, which are frequently associated with neuropathic pain. Anticholinergic adverse effects (AEs), including dry mouth, constipation, and drowsiness, are possible with TCAs, although nortriptyline and desipramine are less likely than amitriptyline to cause AEs. Due to the risk of anticholinergic AEs, it is generally recommended to avoid the use of TCAs in the elderly. Use of TCAs should also be avoided in patients with a history of cardiac arrhythmias. TCAs should be initiated at a low dose, and the dose should be increased every 3 to 5 days until a target dose is reached or AEs become intolerable.
Serotonin/Norepinephrine Reuptake Inhibitors
SNRIs is a class of antidepressant medications that can be used to treat neuropathic pain. These medications include venlafaxine, duloxetine, and milnacipran. An advantage to SNRIs, similar to TCAs, is that they can help improve comorbid depression or anxiety. SNRIs should be used cautiously with other serotonergic medications due to the risk of serotonin syndrome. The most common AE associated with this class is nausea.
The anticonvulsants gabapentin and pregabalin are frequently used in the setting of neuropathic pain management. Gabapentin has been studied for managing various types of neuropathic pain, including diabetic neuropathy and postherpetic neuralgia, and gabapentin case study results have shown a benefit to its use over placebo in managing sciatica.5-7 Pregabalin has also been studied for managing postherpetic neuralgia and diabetic neuropathy, and the drug has shown efficacy in treating pain due to centrally mediated neuropathic pain and due to spinal cord injury.8-11
Along with TCAs, gabapentin is often considered a first-line agent for managing neuropathic pain. Use of pregabalin may be considered after failure with gabapentin due to a lack of efficacy or to intolerable AEs. Gabapentin and pregabalin are started at low doses and titrated every 3 to 7 days until a target dose is reached or AEs prevent further titrations. Both agents require dose adjustments in patients with renal impairment. Horizant (gabapentin enacarbil) and Gralise (gabapentin), extended-release gabapentin formulations, have been FDA-approved for management of postherpetic neuralgia and are designed to improve absorption of gabapentin; however, the cost of these medications is higher than an immediate-release gabapentin product.
Topiramate is another anticonvulsant that may be used for managing neuropathic pain; however, there is a lack of evidence to support the use of topiramate for managing neuropathic pain, and the study results are inconsistent.2 Therefore, topiramate is typically one of the last agents used to treat neuropathic pain. Other anticonvulsants, including carbamazepine, oxcarbazepine, lamotrigine, and lacosamide, have been studied for treating neuropathic pain and the results have been inconsistent, similar to those for topiramate.2
Lidocaine patches are an analgesic alternative for managing localized neuropathic pain. This patch is indicated for treating postherpetic neuralgia and allodynia. One to 3 patches can be used at the same time for up to 12 hours. Because lidocaine patches are associated with a low risk of AEs, they are an option for patients at risk of AEs due to oral therapies.
Due to the risk of serious AEs, including addiction, abuse, and overdose, opioids are generally considered a last-line option for managing neuropathic pain. If used in this setting, using the lowest possible dose is prudent (Online Table 2).
Table 2: Drugs for Managing Neurophathic Pain

Drug Mechanism of Action Advantages Disadvantages Dosing Titration
Tricyclic Antidepressants Amitriptyline Increases serotonin and norepinephrine; blocks sodium channels Sedation; antidepressant effects; less anticholinergic (nortriptyline) Sedation; anticholinergic effects (amitriptyline); drug–drug interactions; cardiac arrhythmias Initial: 25 mg/day
Target: 100 mg/day
Increase by 25 mg intervals every 3-5 days
Nortriptyline Initial: 10 mg daily
Target: 100 mg/day
Increase in 10- mg intervals every 3-5 days
Serotonin/Norepinephrine Reuptake Inhibitors Venlafaxine Increases concentrations of serotonin and norepinephrine by inhibiting the reuptake of serotonin and norepinephrine into the synapse Antidepressant and antianxiolytic effects Nausea; changes in behavior/mood; hepatic impairment (venlafaxine and duloxetine); renal impairment (venlafaxine and milnacipran); blood pressure changes (venlafaxine and milnacipran) Initial: 37.5 mg/day
Target: 225 mg/day
Increase by 37.5 mg in the first week, then increase by 75 mg weekly
Duloxetine Initial: 30 mg/day
Target: 60 mg/day
Increase by 30 mg after first week
Milnacipran Initial: 12.5 mg/day
Target: 100 mg/day
Increase by 12.5 mg twice daily on days 2-3, and by 25 mg twice daily on days 4-7; then 50 mg twice daily
Calcium channel Alpha2-Delta Ligands Gabapentin Binds to alpha2-delta subunit of voltage-gated calcium channels and decreases pain mediators substance P, norepinephrine, and glutamate Inexpensive; sedation Sedation, weight gain, swelling, mental status changes, pharmacokinetic variability Initial: 300 mg/day
Target: 1800-2400 mg/day, divided in 3-4 daily doses
Increase by 300 mg every 3 days
Pregabalin Sedation; consistent pharmacokinetics Expensive; sedation; weight gain; swelling; mental status changes Initial: 150 mg/day, divided
Target: 600 mg/day, divided into 2-3 daily doses
Increase by 150 mg every 7 days
Sodium Channel Blocker
Topiramate Inhibits voltage-gated sodium channels and antagonizes glutamate receptors Promotes weight loss; migraine prophylaxis; typically well- tolerated Mental status changes (trouble with word recall; delayed response); kidney stones; sedation; glaucoma Initial: 25 mg/day
Target: 200 mg/day, divided into 2 daily doses
Increase by 25 mg every 7 days
Topical Analgesic Lidocaine patch Decreases permeability of neurons by sodium ions, which blocks conduction Minimal systemic absorption; localized anesthetic Redness; irritation; skin edema Apply 1-3 patches to painful area; on for 12 hr, then off for 12 hr No titration needed

Pharmacists can play a beneficial role in treating patients suffering from neuropathic pain, regardless of the area of specialty. Pharmacists know and understand the risks and benefits of these medications best, and can play an important role in educating patients and other health care providers. Pharmacists can ensure patients are well informed about the risks and can provide reasonable expectations regarding potential improvement in pain.
Ericka Huckle is a PharmD candidate at the UNC Eshelman School of Pharmacy. Lauren McKnight, PharmD, CPP, BCACP, is a clinical pharmacist practitioner at the University of North Carolina (UNC) Medical Center, Department of Pharmacy, and an assistant professor of Clinical Education at the UNC Eshelman School of Pharmacy.

About the author

Leave a Reply

Your email address will not be published. Required fields are marked *