Psychotherapeutics

Core Concepts

Antipsychotics: dialing down dopamine

The dopamine hypothesis of schizophrenia proposes that excessive dopamine signaling in certain circuits (especially mesolimbic pathways) underlies hallucinations and delusions. Antipsychotics act mainly by blocking D2 dopamine receptors. First-generation ("typical") drugs — e.g., haloperidol, chlorpromazine — are potent D2 antagonists that reduce positive symptoms but can cause extrapyramidal symptoms (EPS): rigidity, restlessness, and, with long-term use, tardive dyskinesia (involuntary movements), because D2 blockade in motor pathways (striatum) is unintended. Second-generation ("atypical") drugs — e.g., clozapine, risperidone — combine D2 blockade with 5-HT2A serotonin receptor antagonism, reducing EPS risk and possibly helping negative symptoms (flat affect, social withdrawal). Clozapine is effective in treatment-resistant cases but requires monitoring — a commonly taught clinical point.

Antidepressants: raising monoamines

Building on the monoamine hypothesis (Chapter 13), antidepressants increase serotonin, norepinephrine, and/or dopamine signaling. SSRIs (e.g., fluoxetine, sertraline) block the serotonin transporter (SERT); SNRIs (e.g., venlafaxine) block SERT and the norepinephrine transporter (NET). Older classes act more broadly: tricyclic antidepressants block SERT and NET but also hit histamine and acetylcholine receptors, causing more side effects (sedation, dry mouth); MAO inhibitors block the enzyme monoamine oxidase that degrades monoamines. All share the therapeutic lag — improvement takes weeks, implicating slow adaptive changes (receptor regulation, neuroplasticity).

Anxiolytics: turning up inhibition

Anxiolytics dampen anxiety by enhancing GABA, the brain's main inhibitory neurotransmitter. Benzodiazepines (e.g., diazepam, alprazolam) bind an allosteric site on the GABA-A receptor — a chloride channel — making it open more readily when GABA binds, increasing inhibition. They act quickly, making them useful for acute anxiety and panic, but they cause tolerance, dependence, and withdrawal risk with continued use, plus memory and coordination impairment. Buspirone, a 5-HT1A partial agonist, is a slower, non-sedating alternative without the same dependence profile.

Mood stabilizers: steadying the swing

Mood stabilizers treat bipolar disorder. Lithium is the classic agent; its mechanism is incompletely understood — commonly taught accounts involve inositol signaling, neurotransmitter balance, and neuroplasticity. Lithium has a narrow therapeutic index (see Topic 1), so blood levels must be monitored; toxicity affects the kidneys, thyroid, and nervous system. Several anticonvulsants (e.g., valproate, lamotrigine) are also used as mood stabilizers. Because manic episodes involve excessive neural activity and dopamine signaling, these drugs dampen excitability rather than boosting any single transmitter.

Stimulants and ADHD medications

Stimulants such as methylphenidate and amphetamine derivatives block the dopamine (DAT) and norepinephrine (NET) transporters, increasing catecholamine signaling. Counterintuitively, in people with ADHD they improve attention and reduce impulsivity rather than causing agitation — reflecting impaired baseline catecholamine function in ADHD circuitry. They carry abuse potential and side effects including appetite suppression and insomnia.

The big picture: drugs as one tool

Psychotherapeutics work best as part of a broader plan that may include psychotherapy and lifestyle changes. Responses vary widely because of genetics (drug-metabolizing enzymes like CYP2D6), age, other medications, and each person's biology. The same drug can help one person and cause intolerable side effects in another; finding the right agent takes trial, monitoring, and time.

How It Works / Step-by-Step Process

Mechanism of an SSRI, from synapse to symptom relief:

1. A presynaptic serotonin neuron releases 5-HT into the cleft; SERT normally pumps it back into the presynaptic terminal.
2. The SSRI blocks SERT, so 5-HT accumulates in the cleft and stimulates postsynaptic receptors longer.
3. Within hours, synaptic 5-HT is elevated — but mood is unchanged.
4. Over 2–6 weeks (commonly taught), the excess 5-HT triggers adaptive changes: receptor downregulation, altered gene expression, and enhanced neuroplasticity in circuits involved in mood and reward.
5. Gradually, prefrontal regulation strengthens, amygdala reactivity calms, and clinical improvement appears.
6. The same lag logic applies across classes: antidepressants are slow, not instant, tools.

Common Confusions