Chapter 18: Psychopharmacology

SIDE EFFECTS IN A NUTSHELL

1. HAM side effects (antiHistamine—sedation, weight gain; antiAdrenergic—hypotension; antiMuscarinic (anticholinergic)—dry mouth, blurred vision, urinary retention, constipation, exacerbation of neurocognitive disorders (i.e., dementias).

   • Found in tricyclic antidepressants (TCAs) and low-potency antipsychotics.

   • Associated with increased risk of falls and delirium in elderly patients.

2. Serotonin syndrome: Confusion, flushing, diaphoresis, tremor, myoclonic jerks, hyperthermia, hypertonicity, rhabdomyolysis, renal failure, and death.

   • This uncommon psychiatric emergency occurs when there is too much serotonin, classically when selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) are combined. As this combination is rarely seen in practice anymore, serotonin syndrome is more commonly seen when a patient is prescribed multiple medications with serotonergic activity (e.g., SSRIs/SNRIs, lithium, trazodone, linezolid, Tramadol, triptans, dextromethorphan, St. John's wort, ondansetron), or other illicit drugs with serotonergic activity (e.g., cocaine, MDMA, amphetamine).

   • Treatment: Stop medications, supportive care, possibly use cyproheptadine or even ECT.

3. Hypertensive crisis: Caused by a buildup of stored catecholamines (norepinephrine); triggered by the combination of MAOIs with tyramine-rich foods (e.g., red wine, cheese, chicken liver, cured meats) or with sympathomimetics. Treated with IV phentolamine or sublingual nifedipine.

4. Extrapyramidal side effects (EPS): Parkinsonism—mask-like face, cogwheel rigidity, bradykinesia, pill-rolling tremor; akathisia—restlessness, need to move, and agitation; dystonia—sustained, painful contraction of muscles of neck, tongue, eyes, diaphragm.

   • Occur more frequently with high-potency, typical (first generation) antipsychotics, but can also be seen with atypical (second generation) antipsychotics.

   • Reversible.

   • All EPS can be treated with benztropine (Cogentin), although for akathisia, beta-blockers such as propranolol are first-line.

   • Occur within hours to days of starting medications or increasing doses.

   • In rare cases, can be life threatening (e.g., dystonia of the diaphragm causing asphyxiation).

   • Drug-induced parkinsonism should be differentiated from primary neurodegenerative Parkinson disease.

5. Hyperprolactinemia: Occurs with high-potency, typical (first generation) antipsychotics and risperidone.

6. Tardive dyskinesia (TD): Choreoathetoid (involuntary, irregular, and repetitive) muscle movements, usually of the mouth and tongue (can affect extremities, as well).

   • Occurs after years of antipsychotic use (more likely with high-potency, first-generation antipsychotics).

   • Usually irreversible.

7. Neuroleptic malignant syndrome: Mental status changes, fever, tachycardia, hypertension, tremor, hyporeflexia, elevated creatine phosphokinase (CPK), “lead pipe” rigidity.

   • Can be caused by any antipsychotic after a short or long time (increased with high-potency, typical antipsychotics).

   • A medical emergency with up to a 20% mortality rate.

   • Treatment includes dantroline, bromocriptine, and ECT in emergencies.

8. Drug interactions: Cytochrome P450 is a group of enzymes in the liver that metabolizes many common drugs, including psychiatric medications.

   • Some medications induce the system, in other words the system metabolizes medications faster—drug levels decrease.

   • Some medications inhibit the system, in other words the system metabolizes medications more slowly—drug levels increase.

   • Common cytochrome P450 enzymes important in metabolizing psychiatric medications include CYP3A4, CYP2D6, CYP1A2, CYP2C9, and CYP2C19.

   • For example: A patient with schizophrenia who smokes a pack of cigarettes a day is prescribed olanzapine. The tobacco induces CYP450 enzyme to metabolize the ...