Nonpsychiatric indications for antidepressants and antipsychotics

Multiple uses for antidepressants and antipsychotics

One of the first medications discovered to have antidepressant effects was iproniazid, a monoamine oxidase inhibitor (MAOI) initially used to treat tuberculosis.⁴ Since then, numerous classes of antidepressant medications have been developed that capitalize on monoamine reuptake through several different mechanisms of action. These drugs can be grouped into subclasses that include selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, MAOIs, and others. True to their roots in iproniazid, these medications can have a myriad of effects not limited to mental health and can therefore be beneficial for a variety of comorbid conditions.

As was the case with antidepressants, the first medication approved in the antipsychotic class, chlorpromazine, was serendipitously discovered to treat psychosis and agitation after being approved and used to treat presurgical apprehension.⁵ The term “antipsychotic” is almost a misnomer given these agents’ broad pharmacology profiles and impact on various mental illnesses, including bipolar disorder, depressive disorders, anxiety disorders, and many other mental conditions. First-generation antipsychotics (FGAs) were the first to enter the market; they work primarily by blocking dopamine-2 (D2) receptors. Second-generation antipsychotics have less movement-based adverse effects than FGAs by having higher affinity for serotonin 5-HT2A receptors than for D2 receptors. However, they tend to carry a higher risk for weight gain and metabolic syndrome.

Antidepressants and antipsychotics are widely utilized in psychiatry. Many have been found to have additional uses beyond their original FDA-approved indication and can therefore be beneficial for a variety of comorbid conditions.

One limitation of using psychiatric medications for nonpsychiatric indications is that different doses of antidepressants and antipsychotics are typically targeted for different indications based on receptor binding affinity. A common example of this is trazodone, where doses below 100 mg are used as needed for insomnia, but higher doses ranging from 200 to 600 mg/d are used for depression. Another important consideration is DDIs. For example, the possibility of adding an agent such as fluoxetine to a complex pain regimen for fibromyalgia could impact the clearance of other agents that are cytochrome P450 (CYP) 2D6 substrates due to fluoxetine’s potent inhibition of the enzyme.^6,7 Table 1^6-51, Table 2^52-68, Table 3^69-107, and Table 4^108-123 provide information on select antidepressants, while Table 5^124-140 and Table 6^141-171 provide information on select antipsychotics. Each table lists psychiatric and nonpsychiatric indications for the respective medications, including both FDA-approved (where applicable) and common off-label uses. Most of the indications listed are for adult use only, unless otherwise noted.

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