Most psychiatric disorders remain without well-established biological substrates; however, standardized diagnostic nosology has gained acceptance, primarily in the form of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). As with other areas of medicine, there is no substitute for a careful diagnostic evaluation using externally validated diagnostic criteria. Whenever possible, the diagnostic evaluation should draw on a comprehensive database that includes family members, previous or concurrent providers, and other sources of information, and the evaluation should focus more on longitudinal data than just acute presentation.

An understanding of the basic pharmacokinetics and pharmacodynamics of psychotropic drugs is required for their safe and effective utilization. With the exception of lithium (which is an element), most psychotropic drugs are lipophilic polycyclic amines. These drugs interact with neurotransmitter-binding sites, which confer their psychotropic effects. For example, most antidepressants act by allosteric binding to catecholamine- or indolamine-uptake binding sites (or with the monoaminergic catalytic enzyme monoamine oxidase), which enhances the synaptic availability of monoamines such as norepinephrine and serotonin. These effects can produce direct antidepressant actions but also may produce side effects such as nausea or nervousness. These drugs also interact with muscarinic cholinergic-binding sites, producing significant side effects such as dry mouth, blurred vision, and constipation, and with histamine-binding sites, producing drowsiness and weight gain. The relative profile of receptor binding affinities will allow the clinician to predict both the beneficial effects and side effects of specific drugs.

Most psychotropic drugs are fairly rapidly and completely absorbed from oral and intramuscular sites and, because of their relatively high lipid solubility, readily cross the blood–brain barrier. Intramuscular administration yields rapid absorption and distribution and bypasses first-pass hepatic metabolism. Therefore, plasma levels are achieved much more rapidly. Intramuscular delivery of antipsychotic drugs (e.g., haloperidol, olanzapine, ziprasidone) or antianxiety agents (e.g., lorazepam) are reserved primarily for the acute management of agitated and psychotic patients. An exception to this is the use of haloperidol or fluphenazine decanoate; both drugs are provided in oil suspension for long-term treatment of psychotic conditions. They require injection every 2–4 weeks and are given to patients who have problems with treatment compliance.

Most psychotropic drugs have high levels of protein (e.g., α1 glycoproteins) binding. Notable exceptions include lithium and venlafaxine. Therefore, drug interactions could occur at the level of protein binding, in which case these drugs will displace (and be displaced by) other drugs with significant binding. This can result in unexpected toxicities; therefore, clinicians should take a careful drug history whenever they plan to prescribe a new drug to a patient.

With the exception of lithium, all psychotropic drugs are metabolized, at least in part, via cytochrome enzymes. After one or more metabolic steps, water-soluble products (e.g., glucuronides) are formed and eliminated via the kidney. Certain psychopharmacologic agents may induce or inhibit metabolism by cytochrome P-450 (CYP) enzymes. For example, car bamazepine can induce CYP 3A4, 2B1, and 2B2 enzymes, whereas certain serotonin selective reuptake inhibitor (SSRI) antidepressants may inhibit metabolism via CYP 2D6. These metabolic interactions must be considered when drugs are coadministered.

Most psychotropic drugs produce widely varying plasma levels, and monitoring may be helpful. However, plasma-level ranges are established only with certain tricyclic antidepressants (e.g., imipramine, desipramine, nortriptyline), with antipsychotics such as haloperidol and clozapine, and with lithium. Because of the narrow therapeutic index, plasma-level monitoring of lithium is part of accepted practice. With other drugs, where there are no established plasma level-response relationships, plasma-level monitoring can be used to check compliance or when severe side effects suggest abnormally increased levels. In addition, plasma levels may clarify a situation in which one drug may be increasing or decreasing the level of another. For example, an SSRI such as paroxetine may elevate plasma levels of other drugs that are metabolized by CYP 2D6 (e.g., haloperidol). Unexpected side effects could occur that would be clarified by a plasma-level measurement.