NOVEL TREATMENTS

There are no published double-blind controlled studies of almost all novel treatments in bipolar disorder. Most inferences have been drawn from case reports and case series, or systematic open studies.

Thyroxine continues to be used despite a lack of strong evidence for its efficacy in bipolar disorder. Thyroxine has been used in refractory rapid cycling disorder with or without a raised TSH. The doses of Thyroxine have varied from 50 to 150 micrograms, and there is little evidence to support the use of hypermetabolic doses.

Risperidone shows some promise in bipolar disorder with or without psychosis, but there have been recent reports of mania induced with doses about 6 mg per day. Increasingly, in many centres, Risperidone has become a front-line neuroleptic in the adjunctive treatment of mania. Many clinicians use Flupenthixol, which at low doses may have a profile similar to Risperidone, as an adjunctive treatment in bipolar disorder.

There is reasonably good and growing evidence that Clozapine is effective both in refractory depression and mania in bipolar disorder, with or without psychosis, but its use has been restricted by its potential hematological adverse effects and lack of ready availability for bipolar disorder in many parts of the world.

Calcium channel blockers, like verapamil, have been well studied, and although they held initial promise, there is little evidence to support their use as a front-line mood stabilizer. There are case reports of the usefulness of the lipophilic calcium channel blocker, Nimodipine. (Bowden, 1996)

Lamotrigine (Calabrese et al, 1996; Yatham et al, 1997; Kusumakar et al, 1997) has shown promise in bipolar depression and rapid cycling bipolar disorder in open studies. Double-blind studies are currently being conducted. Doses ranging from 50 mg to 300 mg per day have been used. It is wise to start at a low dose of 12.5 mg per day, titrated up slowly. There is early evidence, albeit in open studies, that, when combined with Divalproex or Lithium, patients may often respond to doses between 75 mg to 150 mg per day. Monitoring of liver functions, PT & PTT, CBC and skin rash is essential. The appearance of skin rash could herald a Steven-Johnson’s Syndrome or a severe dermatological crisis.

Gabapentin has been used successfully in bipolar depression and publication of a recent open trial is awaited. It has a very good side effect profile and is relatively safe to use with most psychotropic medications by virtue of the fact that it is virtually totally excreted by the kidneys. Dose ranges of Gabapentin used in bipolar disorder have ranged from 600 mg to 1200 mg per day, with a low starting dose titrated up over a few days. Systematic studies are underway with Gabapentin.

Adrenergic blockers, calcium channel blockers, acetazolamide, sex hormones, choline, and tryptophan have been used in bipolar disorder, although the evidence for their efficacy is weak at this stage. (Bowden, 1996) Light therapy, although not rigorously studied, has been reported to be useful in some patients with bipolar depression. Future directions include the study of the efficacy of dopamine agonists, peptidomimetics and antagonists, and drugs that target second messenger systems and transcription factors.

References
Bowden CL. 1996. Role of Newer Medications for Bipolar Disorder. J Clin Psychopharmacology. 16. 2. Suppl 1. 48S-55S.

Calabrese JR, Fatemi SH, Woyshville MJ et al. 1996. Lamotrigine in Rapid Cycling Bipolar Disorder. Amer J. Psychiatry. 153. 1236.

Kusumakar V and Yatham LN. 1997. An Open Study of Lamotrigine in Refractory Bipolar Depression. Brief Report submitted for publication.

Yatham LN and Kusumakar V. 1997. Lamotrigine in Bipolar Depression. Letter in press, American Journal of Psychiatry.