Psychiatric Medications

Antidepressants

Antidepressants are first-line pharmacotherapy for major depressive disorder, anxiety disorders, and several other conditions. All classes require 2–6 weeks for therapeutic onset and are generally used for 6–12 months after symptom remission (longer for recurrent depression).

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are the most commonly prescribed antidepressants due to their favorable side effect profile and safety in overdose. They block serotonin reuptake at the serotonin transporter (SERT), increasing synaptic serotonin availability.

Medication	Typical Dose Range	Half-Life	Notable Features
Fluoxetine	20–80 mg/day	4–6 days (active metabolite: 7–15 days)	Least withdrawal risk; activating; highest FDA pregnancy category data
Sertraline	50–200 mg/day	~26 hours	Broad anxiety disorder indication; gastrointestinal side effects common
Citalopram	20–40 mg/day	~36 hours	QTc prolongation >40 mg; drug-drug interactions minimal
Escitalopram	10–20 mg/day	~30 hours	Most selective SSRI; fewer drug interactions than citalopram
Paroxetine	20–60 mg/day	~21 hours	Most anticholinergic; highest weight gain; most sexual dysfunction; significant withdrawal syndrome
Fluvoxamine	100–300 mg/day	~15 hours	FDA-approved for OCD; significant CYP450 interactions

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs block reuptake of both serotonin and norepinephrine via SERT and NET.

Medication	Typical Dose Range	Mechanism	Unique Features
Venlafaxine XR	75–225 mg/day	SERT > NET at low doses; NET inhibition at higher doses	Nausea common at initiation; blood pressure monitoring required at > 150 mg/day
Duloxetine	60–120 mg/day	Balanced SERT/NET inhibition	Also FDA-approved for neuropathic pain, fibromyalgia, chronic musculoskeletal pain
Desvenlafaxine	50 mg/day	Active metabolite of venlafaxine	Minimal CYP450 metabolism; dose adjustment in renal impairment
Levomilnacipran	40–120 mg/day	NET > SERT inhibition (most noradrenergic SNRI)	Also FDA-approved for fibromyalgia; nausea, dizziness common

Serotonin Modulators (Atypicals)

Medication	Mechanism	Typical Dose	Comments
Bupropion	NDRI (NET/DAT inhibition)	150–450 mg/day	No sexual side effects; activating; seizure risk at high doses; contraindicated in ED, seizure disorders
Mirtazapine	Alpha-2 antagonist; 5-HT2/5-HT3 antagonist	15–45 mg/day	Sedating; appetite stimulation; no sexual side effects; lower GI side effects
Trazodone	SERT inhibitor + 5-HT2A antagonist	150–400 mg/day (antidepressant); 25–100 mg (sleep)	Priapism risk (rare); sedation; cardiac effects (do not use with MAOI)
Vilazodone	SSRI + 5-HT1A partial agonist	10–40 mg/day	Must take with food (50% increase in absorption); GI side effects
Vortioxetine	SERT inhibitor + multiple serotonin receptor modulation	5–20 mg/day	Cognitive-enhancing effects reported; minimal weight gain; nausea dose-dependent

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs irreversibly inhibit monoamine oxidase (MAO-A and/or MAO-B), reducing the breakdown of serotonin, norepinephrine, and dopamine. They are reserved for treatment-resistant depression due to dietary restrictions and drug interactions.

Medication	Selectivity	Dose Range	Dietary Restriction
Phenelzine	Non-selective (MAO-A + MAO-B)	45–90 mg/day	Strict tyramine-free diet; avoid aged cheeses, cured meats, fermented foods, beer, wine
Tranylcypromine	Non-selective	30–60 mg/day	Same as phenelzine; amphetamine-like structure may provide stimulation
Selegiline (transdermal)	MAO-B selective (patch); MAO-A at higher doses	6–12 mg/day (patch)	No dietary restrictions at 6 mg/day patch

Tricyclic Antidepressants (TCAs)

TCAs block reuptake of serotonin and norepinephrine at SERT and NET, but also affect histamine, acetylcholine, and alpha-1 receptors, leading to significant side effects.

Medication	Typical Dose	Side Effect Profile	Toxicity
Nortriptyline	50–150 mg/day	Least anticholinergic; preferred in older adults	Narrow therapeutic index; lethal in overdose
Amitriptyline	75–300 mg/day	Strong anticholinergic; sedation; weight gain	Lethal in overdose (cardiotoxicity)
Clomipramine	100–250 mg/day	Strong anticholinergic; also for OCD	Lethal in overdose
Imipramine	75–300 mg/day	Moderate anticholinergic; bedwetting in children	Lethal in overdose

Side Effect Comparison Across Antidepressant Classes

Side Effect	SSRIs	SNRIs	TCAs	MAOIs	Bupropion	Mirtazapine
Nausea/GI	High (10–30%)	High (20–35%)	Moderate	Moderate	Low	Very low
Sexual dysfunction	High (30–60%)	High (30–50%)	Moderate (20–30%)	High	Very low	Very low
Weight gain	Moderate (paroxetine > others)	Low-moderate	Moderate-high	Moderate	Weight loss	High
Sedation	Low (paroxetine moderate)	Low	High	Low-moderate	None (activating)	High
Insomnia/activation	Moderate	Moderate	Low	High	Moderate	Low
QTc prolongation	Citalopram dose-dependent	Low	High (overdose)	Low	Low	Low
Seizure risk	Very low	Very low	Moderate (high dose)	Low	Dose-dependent	Very low
Hypertension	None	Dose-dependent	Orthostatic	Hypertensive crisis (with tyramine)	Yes	Orthostatic

Antidepressant Discontinuation Syndrome

Abrupt discontinuation of antidepressants can cause a withdrawal-like syndrome. Risk varies by medication half-life.

Medication	Discontinuation Risk	Symptoms	Duration
Paroxetine	Highest	Dizziness, nausea, fatigue, “brain zaps,” irritability, headache	1–3 weeks
Venlafaxine	High	Similar plus visual disturbances, sensory dysesthesias	1–2 weeks
Fluoxetine	Lowest	Minimal; protective due to long half-life	Not typical
Sertraline	Moderate	Mild dizziness, nausea, irritability	1–2 weeks
TCAs	High	Cholinergic rebound: nausea, vomiting, sweating, insomnia	1–2 weeks

Management: slow taper over weeks to months; switch to fluoxetine (for short half-life agents) before taper.

Antipsychotics

Antipsychotics are primarily used for schizophrenia, bipolar mania, and adjunctive treatment of depression. They are divided into first-generation (typical) and second-generation (atypical).

Typical (First-Generation) Antipsychotics

Mechanism: D2 dopamine receptor antagonism.

Medication	Potency	Typical Dose Range (mg/day)	EPS Risk	Prolactin Elevation
Haloperidol	High	5–20 mg (PO); 5–10 mg (IM)	High	High
Fluphenazine	High	5–20 mg (PO)	High	High
Perphenazine	Moderate	16–64 mg	Moderate	Moderate
Chlorpromazine	Low	300–800 mg	Low	Moderate
Thioridazine	Low	200–800 mg	Low	Moderate

Atypical (Second-Generation) Antipsychotics

Mechanism: D2 + 5-HT2A antagonism; additional receptor profiles vary.

Medication	Typical Dose Range	Key Receptor Profile	Weight Gain	Metabolic Risk	Sedation	EPS
Risperidone	2–8 mg/day	D2, 5-HT2A	Moderate	Moderate	Low	Dose-dependent (>6 mg)
Olanzapine	10–20 mg/day	D2, 5-HT2A, M1, H1	High	High	High	Low
Quetiapine	150–800 mg/day	D2, 5-HT2A, H1, alpha-1	Moderate-high	Moderate	High	Low
Aripiprazole	10–30 mg/day	D2 partial agonist, 5-HT1A	Low-moderate	Low-moderate	Low	Low
Ziprasidone	80–160 mg/day	D2, 5-HT2A, 5-HT1A	Minimal	Minimal	Low	Low
Lurasidone	40–80 mg/day	D2, 5-HT2A, 5-HT1A	Minimal	Minimal	Low	Akathisia risk
Clozapine	300–900 mg/day	D2 (weak), D4, 5-HT2A, M1, H1	High	High (DM, hyperlipidemia)	High	Very low

Adverse Effects of Antipsychotics

Extrapyramidal Symptoms (EPS)

EPS Type	Onset	Symptoms	Management
Acute dystonia	Hours to days	Muscle spasm (neck, jaw, eyes, tongue); opisthotonos	Anticholinergics (benztropine, diphenhydramine)
Akathisia	Days to weeks	Subjective restlessness; inability to sit still; pacing	Beta-blockers; benzodiazepines; dose reduction
Parkinsonism	Weeks to months	Tremor, rigidity, bradykinesia, shuffling gait	Anticholinergics; dose reduction; switch to atypical
Tardive dyskinesia (TD)	Months to years	Involuntary choreoathetoid movements (face, tongue, limbs)	Discontinue or switch to clozapine; VMAT2 inhibitors (valbenazine, deutetrabenazine)

Metabolic Syndrome

Parameter	Monitoring Frequency	Threshold for Concern
Weight/BMI	Baseline, 4 weeks, 12 weeks, quarterly	> 5% increase at any point
Fasting glucose	Baseline, 12 weeks, annually	> 100 mg/dL (impaired fasting glucose)
Hemoglobin A1c	Baseline, annually	> 5.7%
Fasting lipid panel	Baseline, 12 weeks, annually	LDL > 100; triglycerides > 150
Blood pressure	Baseline, 12 weeks, annually	> 130/80

Prolactin Elevation

Effect	Symptoms	Management
Galactorrhea	Milk discharge from nipples	Switch to prolactin-sparing antipsychotic (aripiprazole, quetiapine, clozapine)
Gynecomastia	Breast enlargement (males)	Aripiprazole augmentation; dose reduction
Amenorrhea	Absent menstrual periods	Endocrine workup; switch antipsychotic
Sexual dysfunction	Decreased libido, erectile dysfunction	Prolactin-sparing agent
Osteoporosis	Bone density loss (long-term)	Monitor BMD; calcium/vitamin D supplementation

Mood Stabilizers

Lithium

Lithium is the gold standard for bipolar I disorder, particularly for preventing manic episodes and reducing suicide risk.

Parameter	Monitoring	Frequency
Serum level	Therapeutic: 0.6–1.2 mEq/L (maintenance); 0.8–1.5 mEq/L (acute)	Every 3–6 months (stable); 5 days after dose change
Renal function	BUN, creatinine, eGFR	Baseline, then every 6–12 months
Thyroid	TSH, free T4	Baseline, then every 6–12 months
Calcium	Serum calcium	Baseline, then annually
ECG	In patients > 50 or with cardiac risk	Baseline
Pregnancy test	For women of childbearing potential	As needed

Toxicity Level	Serum Lithium	Symptoms
Mild	1.5–2.0 mEq/L	Nausea, vomiting, diarrhea, tremor, ataxia, drowsiness
Moderate	2.0–2.5 mEq/L	Confusion, dysarthria, nystagmus, hyperreflexia
Severe	> 2.5 mEq/L	Seizures, coma, renal failure, cardiac dysrhythmia, death

Valproate (Valproic Acid, Divalproex)

Parameter	Target	Frequency
Serum level	50–125 mcg/mL	Every 3–6 months
Liver function	Normal LFTs	Baseline, then every 6–12 months
CBC with platelets	Normal counts	Baseline, then every 6–12 months
Pregnancy test	Negative	Must use birth control due to teratogenicity

Side Effect	Prevalence	Management
Weight gain	> 50%	Dietary counseling; metformin; consider alternative
Tremor	20–30%	Dose reduction; propranolol
Thrombocytopenia	5–20%	Dose-dependent; reversible with dose reduction
Polycystic ovary syndrome (PCOS)	Higher prevalence	Endocrine evaluation; switch to alternative
Hepatotoxicity	< 1% (higher in children < 2)	Monitor LFTs; contraindicated in liver disease

Lamotrigine

Parameter	Detail
Indication	Bipolar depression prophylaxis (not acute mania)
Dose titration	25 mg/day x 2 weeks; 50 mg/day x 2 weeks; 100 mg/day x 1 week; target 200 mg/day
Mechanism	Voltage-gated sodium channel blockade; glutamate release inhibition
Side effects	Dizziness, headache, ataxia, diplopia
Serious risk	Stevens-Johnson syndrome (SJS): 0.8% in adults; slow titration reduces risk
Interaction	Valproate doubles lamotrigine levels; estrogen-containing OCPs halve levels

Anxiolytics

Benzodiazepines

Medication	Onset	Half-Life	Equivalence (Diazepam 10 mg)	Metabolism	Uses
Lorazepam	Intermediate	10–20 h	1 mg	Glucuronidation (safe in hepatic impairment)	Anxiety, panic, status epilepticus
Alprazolam	Rapid	6–12 h	0.5 mg	CYP3A4	Panic disorder, GAD
Clonazepam	Intermediate	30–40 h	0.5 mg	Reduction/acetylation	Panic disorder, seizure disorders
Diazepam	Rapid	40–100 h	10 mg	CYP2C19, demethylation; active metabolites	Alcohol withdrawal, muscle spasm, seizures
Chlordiazepoxide	Slow	50–100 h	25 mg	Demethylation; active metabolites	Alcohol withdrawal

Buspirone

Property	Description
Mechanism	5-HT1A partial agonist
Onset of action	2–4 weeks (not an immediate anxiolytic)
Dose	15–60 mg/day (divided BID/TID)
Advantages	No abuse potential; no sedation; no withdrawal; no sexual dysfunction
Disadvantages	Delayed onset; requires TID dosing; limited efficacy in panic disorder
Efficacy	Comparable to benzodiazepines for GAD; ineffective for panic disorder

Stimulants

Stimulants are first-line pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD).

Medication	Duration	Typical Dose (Adults)	Mechanism	DEA Schedule
Methylphenidate IR	3–4 hours	10–40 mg/day (divided BID/TID)	DAT/NET reuptake blockade	II
Methylphenidate ER/OROS (Concerta)	10–12 hours	18–72 mg/day	DAT/NET reuptake blockade	II
Dexmethylphenidate (Focalin XR)	10–12 hours	5–30 mg/day	DAT/NET reuptake blockade (d-isomer)	II
Amphetamine mixed salts (Adderall XR)	10–12 hours	5–40 mg/day	DAT/NET reuptake blockade + MAO (trace amine)	II
Lisdexamfetamine (Vyvanse)	10–14 hours	30–70 mg/day	Prodrug metabolized to dextroamphetamine; abuse-deterrent	II

Side Effects of Stimulants

Side Effect	Prevalence	Management
Decreased appetite	20–40%	Take with/after food; calorie-dense meals; drug holidays
Insomnia	15–30%	Avoid evening dosing; consider immediate-release for late-day coverage
Cardiovascular effects (increased HR, BP)	5–15%	Monitor vitals; avoid in uncontrolled hypertension; screen with ECG
Irritability/rebound	10–20%	Extended-release formulations; guanfacine/clonidine augmentation
Growth suppression (children)	5–10%	Monitor growth curves; drug holidays; consider non-stimulant alternative

Non-Stimulant ADHD Medications

Medication	Mechanism	Onset	Dose	Notes
Atomoxetine	NET reuptake inhibitor	4–8 weeks	40–100 mg/day	First-line for comorbid anxiety/SUD; hepatic metabolism
Guanfacine XR	Alpha-2A agonist	2–4 weeks	1–7 mg/day	Also for tics, oppositional behavior; sedation, hypotension
Clonidine XR	Alpha-2 agonist	2–4 weeks	0.1–0.4 mg/day	Sedation, hypotension; QTc monitoring
Bupropion	NDRI	4–6 weeks	150–450 mg/day	Off-label; useful for comorbid depression; seizure risk

Pharmacogenomics in Psychiatry

Pharmacogenomic testing examines genetic variants that affect drug metabolism, response, and adverse effects.

Gene	Enzyme/Protein	Affected Drugs	Clinical Implication
CYP2D6	Cytochrome P450 2D6	SSRIs (fluoxetine, paroxetine, vortioxetine), SNRIs (venlafaxine), TCAs, antipsychotics (haloperidol, risperidone, aripiprazole)	Poor metabolizers: higher blood levels, increased side effects; ultrarapid metabolizers: lower blood levels, reduced efficacy
CYP2C19	Cytochrome P450 2C19	SSRIs (citalopram, escitalopram, sertraline), TCAs	Poor metabolizers: increased citalopram/escitalopram levels; reduce dose
CYP2C9	Cytochrome P450 2C9	NSAIDs, warfarin, several psychiatric drugs	Less impact on psychiatric medications
SLC6A4	Serotonin transporter (5-HTT)	SSRIs	5-HTTLPR short allele may predict poorer SSRI response
HTR2A	5-HT2A receptor	Antipsychotics, some antidepressants	Variants may predict response and side effect risk
COMT	Catechol-O-methyltransferase	Dopamine-affecting medications	Val158Met variant affects prefrontal dopamine

Pregnancy and Lactation Considerations

Antidepressant Use in Pregnancy

Medication	Pregnancy Risk	Lactation Risk	Comments
Sertraline	Generally preferred	Low levels in breast milk	Most data support safety
Fluoxetine	Generally safe	Long half-life; lower preferred	Guard against neonatal adaptation syndrome
Paroxetine	Avoid if possible	Low levels	Small increased risk of cardiac malformations (absolute risk < 1%)
Bupropion	Avoid in first trimester?	Low levels	Possible increased risk for left heart defects
TCAs	Generally safe	Low levels	Nortriptyline preferred

Mood Stabilizers in Pregnancy

Medication	Pregnancy Category	Teratogenicity	Management
Lithium	High risk	Ebstein anomaly (0.05–0.1% absolute risk; 10–20x baseline)	Fetal echocardiography at 16–18 weeks; limit to 1st trimester; mood episode risk vs. teratogenicity
Valproate	Contraindicated	Neural tube defects (5–9%); neurodevelopmental delay (IQ reduction)	Avoid in women of childbearing potential; require effective contraception
Lamotrigine	Generally favorable	Cleft palate (0.3–0.4%)	Steady levels throughout pregnancy due to volume changes
Atypical antipsychotics	Mixed evidence	Slightly increased risk of malformations	Data growing; olanzapine, quetiapine, aripiprazole most studied

Key Pregnancy Principles

Principle	Rationale
Untreated maternal psychiatric illness is itself a risk	Depression, mania, and psychosis during pregnancy are associated with poor outcomes (low birth weight, preterm birth, impaired attachment)
Monotherapy at the lowest effective dose	Polypharmacy and high doses increase fetal exposure
Avoid abrupt discontinuation	Relapse risk is high; gradual cross-taper is preferred
Use medications with the most reproductive safety data	Sertraline, fluoxetine, lamotrigine, and some antipsychotics have more data than newer agents
Involve prescriber and obstetrician	Collaborative decision-making minimizes risk