Pregnancy

• Risk Category D [positive evidence of risk to human fetus; potential benefits may still justify its use during pregnancy]

• Increased risk of cleft lip/palate

• Use in women of childbearing potential requires weighing potential benefits to the mother against the risks to the fetus

• Hypospadia has occurred in some male infants whose mothers took topiramate during pregnancy

✽ Lack of convincing efficacy for treatment of bipolar disorder suggests risk/benefit ratio is in favor of discontinuing topiramate in bipolar patients during pregnancy

✽ For bipolar patients, topiramate should generally be discontinued before anticipated pregnancies

• Antiepileptic Drug Pregnancy Registry: (888) 233–2334

• Taper drug if discontinuing

✽ For bipolar patients, given the risk of relapse in the postpartum period, mood stabilizer treatment, especially with agents with better evidence of efficacy than topiramate, should generally be restarted immediately after delivery if patient is unmedicated during pregnancy

✽ Atypical antipsychotics may be preferable to topiramate if treatment of bipolar disorder is required during pregnancy

• Bipolar symptoms may recur or worsen during pregnancy and some form of treatment may be necessary

• Seizures, even mild seizures, may cause harm to the embryo/fetus

Breast Feeding

• Some drug is found in mother’s breast milk

✽ Recommended either to discontinue drug or bottle feed

• If drug is continued while breast feeding, infant should be monitored for possible adverse effects

• If infant shows signs of irritability or sedation, drug may need to be discontinued

✽ Bipolar disorder may recur during the postpartum period, particularly if there is a history of prior postpartum episodes of either depression or psychosis

✽ Relapse rates may be lower in women who receive prophylactic treatment for postpartum episodes of bipolar disorder

• Atypical antipsychotics and anticonvulsants such as valproate may be safer and more effective than topiramate during the postpartum period when treating nursing mother with bipolar disorder

TOPIRAMATE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Treatment-resistant bipolar disorder

• Patients who wish to avoid weight gain

Potential Disadvantages

• Efficacy in bipolar disorder uncertain

• Patients with a history of kidney stones or risks for metabolic acidosis

Primary Target Symptoms

• Incidence of seizures

• Unstable mood

Pearls

• Side effects may actually occur less often in pediatric patients

• Has been studied in a wide range of psychiatric disorders, including bipolar disorder, posttraumatic stress disorder, binge-eating disorder, obesity, and others

• Some anecdotes, case series, and open-label studies have been published and are widely known suggesting efficacy in bipolar disorder

✽ However, randomized clinical trials do not suggest efficacy in bipolar disorder; unfortunately these important studies have not been published by the manufacturer, who has dropped topiramate from further development as a mood stabilizer, though this is not widely known

✽ Misperceptions about topiramate’s efficacy in bipolar disorder have led to its use in more patients than other agents with proven efficacy, such as lamotrigine

✽ Due to reported weight loss in some patients in trials with epilepsy, topiramate is commonly used to treat weight gain, especially in patients with psychotropic drug-induced weight gain

✽ Weight loss in epilepsy patients is dose-related with more weight loss at high doses (mean 6.5 kg or 7.3% decline) and less weight loss at lower doses (mean 1.6 kg or 2.2% decline)

✽ Changes in weight were greatest in epilepsy patients who weighed the most at baseline (>100 kg), with mean loss of 9.6 kg or 8.4% decline, while those weighing <60 kg had only a mean loss of 1.3 kg or 2.5% decline

✽ Long-term studies demonstrate that weight losses in epilepsy patients were seen within the first 3 months of treatment and peaked at a mean of 6 kg after 12–18 months of treatment; however, weight tended to return to pretreatment levels after 18 months

✽ Some patients with psychotropic drug-induced weight gain may experience significant weight loss (>7% of body weight) with topiramate up to 200 mg/day for 3 months, but this is not typical, is not often sustained, and has not been systemically studied

• Early studies suggest potential efficacy in binge-eating disorder

• The combination of topiramate and phentermine is approved as a treatment for obesity (see phentermine-topiramate); the combination is also being studied in diabetes and sleep apnea

Suggested Reading

Johnson BA, Ait-Daoud N. Topiramate in the new generation of drugs: efficacy in the treatment of alcoholic patients. Curr Pharm Des 2010;16(19):2103–12.

Kramer CK, Leitao CB, Pinto LC, et al. Efficacy and safety of topiramate on weight loss: a meta-analysis of randomized controlled trials. Obes Rev 2011;12(5):e338–47.

Ormrod D, McClellan K. Topiramate: a review of its use in childhood epilepsy. Paediatr Drugs 2001;3:293–319.

Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia 2000;41(Suppl 1):S3–9.

Suppes T. Review of the use of topiramate for treatment of bipolar disorders. J Clin Psychopharmacol 2002;22:599–609.

TRANYLCYPROMINE

TRANYLCYPROMINE: THERAPEUTICS

Brands

• Parnate

see index for additional brand names

Generic?

Yes

Class

• Monoamine oxidase inhibitor (MAOI)

Commonly Prescribed for

(bold for FDA approved)

• Major depressive episode without melancholia

• Treatment-resistant depression

• Treatment-resistant panic disorder

• Treatment-resistant social anxiety disorder

How the Drug Works

• Irreversibly blocks monoamine oxidase (MAO) from breaking down norepinephrine, serotonin, and dopamine

• This presumably boosts noradrenergic, serotonergic, and dopaminergic neurotransmission

✽ As the drug is structurally related to amphetamine, it may have some stimulant-like actions due to monoamine release and reuptake inhibition

How Long Until It Works

• Some patients may experience stimulant-like actions early in dosing

• Onset of therapeutic actions usually not immediate, but often delayed 2–4 weeks

• If it is not working within 6–8 weeks, it may require a dosage increase or it may not work at all

• May continue to work for many years to prevent relapse of symptoms

If It Works

• The goal of treatment is complete remission of current symptoms as well as prevention of future relapses

• Treatment most often reduces or even eliminates symptoms, but not a cure since symptoms can recur after medicine stopped

• Continue treatment until all symptoms are gone (remission)

• Once symptoms gone, continue treating for 1 year for the first episode of depression

• For second and subsequent episodes of depression, treatment may need to be indefinite

• Use in anxiety disorders may also need to be indefinite