Psychopharmacology

In the human brain, information is transmitted in the form of bioelectrical impulses and chemical signaling molecules. These molecules, called neurotransmitters, are protein molecules used by neurons to emit a specific signal. The signals are picked up in the plasma membrane of adjacent neurons by receptors, which are complexes of protein subunits responsible for sensing relevant stimuli and setting in motion the cellular machinery required to produce the desired response.

Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. In effect, there is an increased concentration of neurotransmitters in the synapse. Histaminic, muscarinic, and adrenergic receptors are also blocked, leading to a wide array of side effects. For decades, TCAs have been utilized for depression and are considered alternative antidepressant options to selective serotonin reuptake inhibitors (SSRIs). Full effects take a latent period of around 2–3 weeks. Overdose can lead to cardiac toxicity, seizures, and coma. Other uses include treatment for anxiety disorders, chronic pain syndrome, and nocturnal enuresis.

Second-generation antipsychotics (SGAs) are also called atypical antipsychotics. Medications in this class include aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lumateperone, lurasidone, olanzapine, paliperidone, pimavanserin, quetiapine, risperidone, and ziprasidone. The SGAs act primarily by antagonizing dopamine (D2) and serotonin (5-hydroxytryptamine 2 (5-HT2)) receptors. Clinical indications include the treatment of schizophrenia, bipolar disorder, and treatment-resistant depression. In comparison to 1st-generation antipsychotics (FGAs), the SGAs cause fewer extrapyramidal symptoms but more metabolic adverse effects.

Monoamine oxidase inhibitors are a class of antidepressants that inhibit the activity of monoamine oxidase (MAO), thereby increasing the amount of monoamine neurotransmitters (particularly serotonin, norepinephrine, and dopamine). The increase of these neurotransmitters can help in alleviating the symptoms of depression. Selective inhibitors of MAO type B can also be used for the treatment of Parkinson disease. Other uses include for bulimia nervosa and panic disorder. The major adverse effects include serotonin syndrome and hypertensive crisis. Special care should be taken to avoid other serotonergic medications and tyramine-containing foods.

Ebstein's anomaly (EA) is a cyanotic congenital heart disease (CHD) characterized by the downward displacement of the septal and posterior leaflets of the tricuspid valve (TV). Ebstein's anomaly accounts for less than 1% of all cases of CHD. Maternal use of lithium is a common cause of EA. Clinical presentation varies, with the most common symptom being cyanosis. The age of presentation varies from in utero to adulthood and is proportional to the severity of the TV displacement, most cases present during adolescence. Ebstein's anomaly presents with multiple comorbidities, especially Wolff-Parkinson-White syndrome. The diagnosis is confirmed by echocardiography and definitive treatment is surgical. Patients who are managed appropriately still have a reduced life expectancy.

Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. The drug class of benzodiazepines has anxiolytic, muscle-relaxant, hypnotic, sedative, and anticonvulsant properties. These agents are not generally recommended for long-term use, as patients can develop physiological and psychological dependence. Side effects may include cognitive impairment, somnolence, and respiratory depression.

Sedative, hypnotic, and anxiolytic agents include benzodiazepines (BZDs), barbiturates, and other hypnotics. Symptoms of intoxication include ataxia, minor respiratory depression, and short-term memory loss. Withdrawal symptoms include insomnia, anxiety, psychosis, and seizures. These drugs are often taken in conjunction with other substances. Chronic use can be managed with medication taper as well as psychosocial interventions.

Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. Drugs from both classes act on dopamine receptors. Notable side effects from antipsychotic agents include movement disorders, dose-related sedation, and metabolic syndrome. A serious long-term side effect to be cautious of is tardive dyskinesia, which is characterized by repetitive involuntary movements.

Antidepressants encompass several drug classes and are used to treat individuals with depression, anxiety, and psychiatric conditions, as well as those with chronic pain and symptoms of menopause. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and many other drugs in a class of their own. Antidepressants are indicated as the 1st-line treatment for anxiety disorders and major depressive disorder (MDD) and are contraindicated in cases of current or recent use of monoamine oxidase inhibitors. Therapeutic response to antidepressants takes 2–4 weeks and complete benefit is not seen until up to 8 weeks, which is attributed to downstream cellular responses necessary for eliciting a physiologic response. In general, serotonin-affecting antidepressants are well tolerated, but caution must be taken while prescribing them in combination with other drugs that inhibit or induce the same hepatic cytochrome P450 enzymes to prevent increased levels of both drugs. An overdose can be life-threatening. It is important to recognize the signs and symptoms of SSRI/SNRI overdose to enable prompt treatment in an emergency setting.