Carbamazepine has been considered to be a reasonable alternative to lithium when the latter is less than optimally efficacious. However, the pharmacokinetic interactions of carbamazepine and its tendency to induce the metabolism of CYP3A4 substrates make it a more difficult drug to use with other standard treatments for bipolar disorder. The mode of action of carbamazepine is unclear, and oxcarbazepine is not effective. Carbamazepine may be used to treat acute mania and also for prophylactic therapy. Adverse effects (discussed in Chapter 24) are generally no greater and sometimes less than those associated with lithium. Carbamazepine may be used alone or, in refractory patients, in combination with lithium or, rarely, valproate.
The use of carbamazepine as a mood stabilizer is similar to its use as an anticonvulsant (see Chapter 24). Dosage usually begins with 200 mg twice daily, with increases as needed. Maintenance dosage is similar to that used for treating epilepsy, ie, 800–1200 mg/d. Plasma concentrations between 3 and 14 mg/L are considered desirable, although the optimal therapeutic range has not been established. Blood dyscrasias have figured prominently in the adverse effects of carbamazepine when it is used as an anticonvulsant, but they have not been a major problem with its use as a mood stabilizer. Overdoses of carbamazepine are a major emergency and should generally be managed like overdoses of tricyclic antidepressants (see Chapter 58).
Lamotrigine is approved as a maintenance treatment for bipolar disorder. Although not effective in treating acute mania, it appears effective in reducing the frequency of recurrent depressive cycles and may have some utility in the treatment of bipolar depression. A number of novel agents are under investigation for bipolar depression, including riluzole, a neuroprotective agent that is approved for use in amyotrophic lateral sclerosis; ketamine, a noncompetitive NMDA antagonist previously discussed as a drug believed to model schizophrenia but thought to act by producing relative enhancement of AMPA receptor activity; and AMPA receptor potentiators.
SUMMARY Antipsychotic Drugs & Lithium Subclass, Drug Mechanism of Action Effects Clinical Applications Pharmacokinetics, Toxicities, Interactions
GENERIC NAME AVAILABLE AS ANTIPSYCHOTIC AGENTS Aripiprazole Abilify Asenapine Saphris Brexpiprazole Rexulti Cariprazine Vraylar Chlorpromazine Generic, Thorazine Clozapine Generic, Clozaril, others Fluphenazine Generic Fluphenazine decanoate Generic, Prolixin Decanoate Haloperidol Generic, Haldol Haloperidol ester Haldol Decanoate Iloperidone Fanapt Loxapine Adasuve Lurasidone Latuda Molindone Moban Olanzapine Generic, Zyprexa Paliperidone Invega Ziprasidone Generic, Geodon MOOD STABILIZERS GENERIC NAME AVAILABLE AS Perphenazine Generic, Trilafon Pimavanserin Nuplazid Pimozide Orap Prochlorperazine Generic, Compazine Quetiapine Generic, Seroquel Risperidone Generic, Risperdal Thioridazine Generic, Mellaril Thiothixene Generic, Navane Trifluoperazine Generic, Stelazine Carbamazepine Generic, Tegretol Divalproex Generic, Depakote Lamotrigine Generic, Lamictal Lithium carbonate Generic, Eskalith Topiramate Generic, Topamax Valproic acid Generic, Depakene PREP AR A TIONS A V AIL ABLE