Calcium Channel Antagonists in Mood Disorders

Abstract

Mood disorders have been the focus of intense research and drug development efforts. Since the introduction of imipramine, the first tricyclic antidepressant, in 1956, numerous compounds have been developed and others have faded from the market. In fact, until the advent of the selective serotonin reuptake inhibitors (SSRIs) in the late 1980s, there had been no clear advances in the pharmacotherapy of mood disorders. Despite the fact that SSRIs offer convenient dosing and a wider index than tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors, the tricyclic antidepressants remain a mainstay of treatment in major depressive disorder and in the depressed phase of bipolar illness. Lithium salts retain their prominent position in the therapy and prophylaxis of bipolar disorder. Two anticonvulsants, sodium valproate and carbamazepine, are acknowledged as alternatives in the almost 50% of bipolar patients who do not respond satisfactorily to lithium (1). Pharmacotherapy remains the most effective mode of treatment in mood disorders, despite the potential toxicity associated with all of these drugs (2). However, out of a concern for serious adverse effects of classic antidepressants, some physicians, especially those involved with primary care in an outpatient setting, may tend to undermedicate patients. It is therefore understandable that efforts continue to develop alternative medications to those already existing. Such drugs would have to be both clinically efficient and safer to use than those currently available. This chapter describes evidence, from both animal experiments and clinical trials, that a group of drugs designated as the calcium channel antagonists has shown promise in this respect. These drugs are similar to lithium in their pharmacodynamic profile of psychotropic activity, but differ in their mechanism of action at the cellular level.