Bipolar disorder as cell membrane dysfunction. Progress toward integrative management

Alternative Medicine Review, June, 2004 by Parris M. Kidd

The anticonvulsant carbamazepine is not suitable as monotherapy to stabilize mood, but does have anti-aggressive properties useful for treating rage attacks. (8)

Lamotrigine is a newer anticonvulsant that significantly improves depression in BD. (4) It is not recommended for mania but can be useful for rapid cycling (see below). However, side effects proscribe its use for children tinder 16 years (Child and Adolescent Bipolar Foundation, 2002).

Lamotrigine has a low switching rate (conversion of depression to manic phases), but potentially serious adverse effects. (55) It causes skin rash in approximately 15 percent of patients or more severe dermatological reactions, including the potentially fatal Stevens-Johnson syndrome (in 0.1 percent of patients). (54) These risks can be decreased by titrating the dose. When lamotrigine is added to valproate, a lower starting dose and slower titration are necessary because valproate can increase serum lamotrigine levels. (55)

Most BD patients require combinations of mood stabilizers to remain in remission. There is evidence that lithium, valproate, and carbamazepine lose efficacy over time and that this tendency is reduced when they are combined. (55) In rapidly cycling patients with frequent depressive episodes, triiodothyronine or possibly other thyroid hormones can augment lithium and the other mood stabilizers. (59) Clearly no existing medication or combination provides exceptional benefit without side effects.

Atypical Antipsychotics

For BD patients refractory to the recognized mood stabilizers, or for those with psychosis, anecdotal experience suggests combining a mood stabilizer with an atypical antipsychotic. These drugs (especially olanzapine and risperidone) are occasionally prescribed for manic states, particularly when rapid control is needed or when delusions or hallucinations are involved.

Olanzapine was tested in a large, still unpublished, eight-week randomized trial with bipolar I patients. (55,60) It was found significantly more effective than placebo for the depression of BD, and even more effective when used in combination with the antidepressant fluoxetine. Olanzapine can cause depression, somnolence, and weight gain. (4)

Risperidone has some evidence supporting its use against psychosis in BD. (55) It can also cause weight gain that averages more than five pounds in three weeks. (4)

When depression of BD is accompanied by marked anxiety or insomnia, a short course of a high potency benzodiazepine such as lorazepam or clonazepam may be helpful. (50)

Antidepressants

Antidepressants are not first-line treatment for the depression of BD or the disorder as a whole. Although they are effective for the depression of BD, they are less so than for unipolar depression and can cause switching to mania or trigger rapid cycling. (50) These risks are greater with tricyclic antidepressants (TCAs) than with selective serotonin reuptake inhibitors (SSRIs). In a review of bipolar trials the rate of switching to mania was 11.2 percent with TCAs. 3.7 percent with SSRIs, and 4.2 percent with placebo (SSRIs versus TCAs, p < 0.01). (50) Therefore, TCAs should be completely avoided and antidepressants as a class provide only limited adjunctive potential. (50) SSRIs such as bupoprion or venlaxafine may be indicated when severe depression does not respond to a mood stabilizer regimen.