Antidepressants

• General principles of antidepressant action
• Antidepressant classes
• Serotonin selective reuptake inhibitors (SSRIs)
• Serotonin norepinephrine reuptake inhibitors (SNRIs)
• Norepinephrine and dopamine reuptake inhibitors (NDRIs)
• Selective norepinephrine reuptake inhibitors (NRIs)
• Alpha 2 antagonists as serotonin and norepinephrine disinhibitors (SNDIs)
• Serotonin antagonist/reuptake inhibitors (SARIs)
• Classic antidepressants: monoamine oxidase inhibitors
• Classic antidepressants: tricyclic antidepressants
• Antidepressant pharmacokinetics
• Trimonoaminergic modulators (triple monoamine modulators, or TMMs)
• Estrogen as a trimonoaminergic, GABA, and glutamate modulator
• L-methylfolate (6-(S)-5-methyltetrahydrofolate, or MTHF) as a trimonoamine modulator (TMM)
• S-adenosyl-methionine (SAMe), MTHF, and methylation
• Thyroid
• Lithium
• Brain stimulation: creating a “perfect storm” in brain circuits of depressed patients
• Psychotherapy
• Antidepressants in clinical practice
• Future treatments for mood disorders
• Summary

Antidepressants

This chapter reviews the pharmacological concepts underlying the use of antidepressant drugs. There are many different classes of antidepressants and dozens of individual drugs. The goal of this chapter is to acquaint the reader with current ideas about how the various antidepressants work. It explains the mechanisms of action of these drugs by building upon general pharmacological concepts introduced in earlier chapters. It also discusses concepts about how to use these drugs in clinical practice, including strategies for what to do if initial treatments fail and how to rationally combine one antidepressant with another or with a modulating agent. Finally, the reader is introduced to several new antidepressants in clinical development.

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FIGURE 12-1 Response. When treatment of depression results in at least 50% improvement in symptoms, it is called a response. Such patients are better but not well. Previously, this was considered the goal of depression treatment.

The treatment of antidepressants in this chapter is at the conceptual level, not at the pragmatic level. The reader should consult standard drug handbooks (such as the companion Essential Psychopharmacology: Prescriber’s Guide) for details of doses, side effects, drug interactions, and other issues relevant to the prescribing of these drugs in clinical practice.