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INTRODUCTION

Four major classes are commonly used in adults: (1) antidepressants (ADs), (2) anxiolytics, (3) antipsychotics, and (4) mood-stabilizing agents. Nonpsychiatric physicians should become familiar with one or two drugs in each of the first three classes so that the indications, dose range, efficacy, potential side effects, and interactions with other medications are well known.

GENERAL PRINCIPLES OF USE

  1. Most treatment failures are due to undermedication and impatience. For a proper medication trial to take place, an effective dose must be taken for an adequate amount of time. For ADs, antipsychotics, and mood stabilizers, full effects may take weeks or months to occur.

  2. History of a positive response to a medication usually indicates that a response to the same drug will occur again. A family history of a positive response to a specific medication is also useful.

  3. Pts who fail to respond to one drug will often respond to another in the same class; one should attempt another trial with a drug that has a different mechanism of action or a different chemical structure. Treatment failures should be referred to a psychiatrist, as should all pts with psychotic symptoms or who require mood stabilizers.

  4. Avoid polypharmacy; a pt who is not responding to standard monotherapy requires referral to a psychiatrist.

  5. Pharmacokinetics may be altered in the elderly, with smaller volumes of distribution, reduced renal and hepatic clearance, longer biologic half-lives, and greater potential for CNS toxicity. The rule with elderly pts is to “start low and go slow.”

  6. Never stop treatment abruptly, especially true for ADs and anxiolytics. In general, medications should be slowly tapered and discontinued over 2–4 weeks.

  7. Review possible side effects each time a drug is prescribed; educate pts and family members about side effects and need for patience in awaiting a response.

ANTIDEPRESSANTS

Useful to group according to known actions on CNS monoaminergic systems (Table 197-1). The selective serotonin reuptake inhibitors (SSRIs) have predominant effects on serotonergic neurotransmission, also reflected in side-effect profile. The TCAs, or tricyclic ADs, affect noradrenergic and, to a lesser extent, serotonergic neurotransmission but also have anticholinergic and antihistaminic effects. Venlafaxine, desvenlafaxine, duloxetine, mirtazapine, vilazodone, vortioxetine, and levomilnacipran have mixed noradrenergic and serotonergic effects. Bupropion is a novel antidepressant that enhances noradrenergic function. Trazodone and amoxapine have mixed effects on serotonin receptors and on other neurotransmitter systems. The monoamine oxidase inhibitors (MAOIs) inhibit monoamine oxidase, the primary enzyme responsible for the degradation of monoamines in the synaptic cleft.

TABLE 197-1ANTIDEPRESSANTS

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