An additional useful distinction is between medications that have primary roles in treatment of, bipolar disorder, vs. those with roles that are per se adjunctive. Primary medications include mood stabilizers, but also include medications that are effective in the manic or depressive phase of the illness. Antipsychotic medications are effectively antimanic. Antidepressant drugs that are approved for major depression are probably effective in alleviating acute bipolar depression, although few have been systematically studied in even one adequate clinical trial. These drugs would qualify as primary treatments.
Drugs that are beneficial for component symptoms that are common in, but not diagnostic of, bipolar disorder, plus ones that may augment response to a primary or mood-stabilizing drug are better viewed as secondary, or adjunctive drugs. Examples include supplementation of antidepressant regimens with thyroid medications or other adjuncts such as pindolol or pramipexole. Others are medications that control anxious symptoms, and/ or improve sleep. These are principally benzodiazepines, or similar agents with GABAergic mechanisms. These are quite important, given the high comorbidity of anxious disorders with bipolar disorder, the high prevalence of anxious symptoms in manic states, and the frequency of sleep disturbance, especially in manic states. This last has probably contributed to early positive reports of antimanic effects of clonazepam and gabapentin [10,11]. More systematic tests of these drugs has failed to provide evidence of monotherapy effectiveness in mania [12, 13]. It is likely that the improvement in sleep secondarily contributed to some improvement in manic symptoms with these drugs, but that the investigators interpreted the improvement as a primary antimanic or mood-stabilizing benefit. Failure to make this distinction will lead to the fallacy of treating the part of the disorder as the whole.
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