PSYCH DRUGS Flashcards
Haloperidol
First-generation antipsychotics (FGAs)
High-potency antipsychotics
Mechanism:
Dopamine-specific antagonism (D2 receptor) (potency of a substance is directly related to the degree of its D2 antagonism)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Delirium Acute agitated states (e.g., patients who are agitated and aggressive due to alcohol and/or illicit drug use) Tourette syndrome OCD (concomitant therapy) Huntington disease
Adverse Effects:
Extrapyramidal symptoms most common in high-potency FGAs
Prolonged QT interval
Neuroleptic malignant syndrome
Lipid soluble –> stored in body fat –> slow to be removed from body.
Dopamine receptor antagonism –> hyperprolactinemia –> galactorrhea, oligomenorrhea, gynecomastia.
Dyslipidemia, weight gain, hyperglycemia.
Antimuscarinic (dry mouth, constipation)
Antihistamine (sedation)
α1-blockade (orthostatic hypotension)
Neuroleptic malignant syndrome.
Hyperthermia or hypothermia (believed to be due to the drug’s effect on the hypothalamus, which leads to inappropriate responses to heat (e.g., lack of sweating/peripheral vasodilation) or cold (e.g., lack of shivering))
Fluphenazine
First-generation antipsychotics (FGAs)
High-potency antipsychotics
Mechanism:
Dopamine-specific antagonism (D2 receptor) (potency of a substance is directly related to the degree of its D2 antagonism)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Delirium Acute agitated states (e.g., patients who are agitated and aggressive due to alcohol and/or illicit drug use) Tourette syndrome OCD (concomitant therapy) Huntington disease
Adverse Effects:
Extrapyramidal symptoms most common in high-potency FGAs
Prolonged QT interval
Neuroleptic malignant syndrome
Lipid soluble –> stored in body fat –> slow to be removed from body.
Dopamine receptor antagonism –> hyperprolactinemia –> galactorrhea, oligomenorrhea, gynecomastia.
Dyslipidemia, weight gain, hyperglycemia.
Antimuscarinic (dry mouth, constipation)
Antihistamine (sedation)
α1-blockade (orthostatic hypotension)
Neuroleptic malignant syndrome.
Hyperthermia or hypothermia (believed to be due to the drug’s effect on the hypothalamus, which leads to inappropriate responses to heat (e.g., lack of sweating/peripheral vasodilation) or cold (e.g., lack of shivering))
Perphenazine
First-generation antipsychotics (FGAs)
High-potency antipsychotics
Mechanism:
Dopamine-specific antagonism (D2 receptor) (potency of a substance is directly related to the degree of its D2 antagonism)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Delirium Acute agitated states (e.g., patients who are agitated and aggressive due to alcohol and/or illicit drug use) Tourette syndrome OCD (concomitant therapy) Huntington disease
Adverse Effects:
Extrapyramidal symptoms most common in high-potency FGAs
Prolonged QT interval
Neuroleptic malignant syndrome
Lipid soluble –> stored in body fat –> slow to be removed from body.
Dopamine receptor antagonism –> hyperprolactinemia –> galactorrhea, oligomenorrhea, gynecomastia.
Dyslipidemia, weight gain, hyperglycemia.
Antimuscarinic (dry mouth, constipation)
Antihistamine (sedation)
α1-blockade (orthostatic hypotension)
Neuroleptic malignant syndrome
Hyperthermia or hypothermia (believed to be due to the drug’s effect on the hypothalamus, which leads to inappropriate responses to heat (e.g., lack of sweating/peripheral vasodilation) or cold (e.g., lack of shivering))
Trifluoperazine
First-generation antipsychotics (FGAs)
High-potency antipsychotics
Mechanism:
Dopamine-specific antagonism (D2 receptor) (potency of a substance is directly related to the degree of its D2 antagonism)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Delirium Acute agitated states (e.g., patients who are agitated and aggressive due to alcohol and/or illicit drug use) Tourette syndrome OCD (concomitant therapy) Huntington disease
Adverse Effects:
Extrapyramidal symptoms most common in high-potency FGAs
Prolonged QT interval
Neuroleptic malignant syndrome
Lipid soluble –> stored in body fat –> slow to be removed from body.
Dopamine receptor antagonism –> hyperprolactinemia –> galactorrhea, oligomenorrhea, gynecomastia.
Dyslipidemia, weight gain, hyperglycemia.
Antimuscarinic (dry mouth, constipation)
Antihistamine (sedation)
α1-blockade (orthostatic hypotension)
Hyperthermia or hypothermia (believed to be due to the drug’s effect on the hypothalamus, which leads to inappropriate responses to heat (e.g., lack of sweating/peripheral vasodilation) or cold (e.g., lack of shivering))
Pimozide
First-generation antipsychotics (FGAs)
High-potency antipsychotics
Mechanism:
Dopamine-specific antagonism (D2 receptor) (potency of a substance is directly related to the degree of its D2 antagonism)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Delirium Acute agitated states (e.g., patients who are agitated and aggressive due to alcohol and/or illicit drug use) Tourette syndrome OCD (concomitant therapy) Huntington disease
Adverse Effects:
Extrapyramidal symptoms most common in high-potency FGAs
Prolonged QT interval
Neuroleptic malignant syndrome
Lipid soluble –> stored in body fat –> slow to be removed from body.
Dopamine receptor antagonism –> hyperprolactinemia –> galactorrhea, oligomenorrhea, gynecomastia.
Dyslipidemia, weight gain, hyperglycemia.
Antimuscarinic (dry mouth, constipation)
Antihistamine (sedation)
α1-blockade (orthostatic hypotension)
Hyperthermia or hypothermia (believed to be due to the drug’s effect on the hypothalamus, which leads to inappropriate responses to heat (e.g., lack of sweating/peripheral vasodilation) or cold (e.g., lack of shivering))
First-generation antipsychotics (FGAs)
High-potency antipsychotics Haloperidol Fluphenazine Perphenazine Trifluoperazine Pimozide
Low-potency antipsychotics
Chlorpromazine
Thioridazine
High-Potency First-Generation Antipsychotics (FGAs)
Haloperidol Fluphenazine Perphenazine Trifluoperazine Pimozide
Mechanism:
Dopamine-specific antagonism (D2 receptor) (potency of a substance is directly related to the degree of its D2 antagonism)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Delirium Acute agitated states (e.g., patients who are agitated and aggressive due to alcohol and/or illicit drug use) Tourette syndrome OCD (concomitant therapy) Huntington disease
Adverse Effects:
Extrapyramidal symptoms most common in high-potency FGAs
Prolonged QT interval
Neuroleptic malignant syndrome
Lipid soluble –> stored in body fat –> slow to be removed from body.
Dopamine receptor antagonism –> hyperprolactinemia –> galactorrhea, oligomenorrhea, gynecomastia.
Dyslipidemia, weight gain, hyperglycemia.
Antimuscarinic (dry mouth, constipation)
Antihistamine (sedation)
α1-blockade (orthostatic hypotension)
Neuroleptic malignant syndrome.
Low-Potency First-Generation Antipsychotics (FGAs)
Chlorpromazine
Thioridazine
Mechanism:
Dopamine antagonism
Anticholinergic
Antihistaminergic (primarily sedative, due to H1 antagonism)
Clinical Use:
Acute agitation
Delirium
Adverse Effects: Anticholinergic effects, sympatholytic effects, metabolic effects, and sedation dominate EPS less common Corneal deposits (chlorpromazine) Retinal deposits (thioridazine) Neuroleptic malignant syndrome.
Chlorpromazine
Low-Potency First-Generation Antipsychotics (FGAs)
Mechanism:
Dopamine antagonism
Anticholinergic
Antihistaminergic (primarily sedative, due to H1 antagonism)
Clinical Use:
Acute agitation
Delirium
Adverse Effects:
Lipid soluble –> stored in body fat –> slow to be removed from body.
Dopamine receptor antagonism –> hyperprolactinemia –> galactorrhea, oligomenorrhea, gynecomastia.
Dyslipidemia, weight gain, hyperglycemia.
Antimuscarinic (dry mouth, constipation)
Antihistamine (sedation)
α1-blockade (orthostatic hypotension)
QT prolongation.
EPS less common
Lenticular and corneal deposits
Neuroleptic malignant syndrome
Thioridazine
Low-Potency First-Generation Antipsychotics (FGAs)
Mechanism:
Dopamine antagonism
Anticholinergic
Antihistaminergic (primarily sedative, due to H1 antagonism)
Clinical Use:
Acute agitation
Delirium
Adverse Effects:
Lipid soluble –> stored in body fat –> slow to be removed from body.
Dopamine receptor antagonism –> hyperprolactinemia –> galactorrhea, oligomenorrhea, gynecomastia.
Dyslipidemia, weight gain, hyperglycemia.
Antimuscarinic (dry mouth, constipation)
Antihistamine (sedation)
α1-blockade (orthostatic hypotension)
QT prolongation.
EPS less common
Retinal deposits
Carries the highest risk of retinitis pigmentosa.
Neuroleptic malignant syndrome
Second-generation antipsychotics (SGAs)
Clozapine Olanzapine Risperidone Quetiapine Amisulpride Ziprasidone Aripiprazole Lurasidone Asenapine Iloperidone Paliperidone
Clozapine
Second-generation antipsychotics (SGAs)
Mechanism:
D2 receptor antagonism (less pronounced than that of FGAs)
5-HT2A receptor antagonism
Interaction with several other receptors (i.e., D3, D4, α-adrenergic, and H1 receptors)
Clinical Use:
Clozapine is used for treatment-resistant psychotic disorders or those with persistent suicidality
Acute therapy for psychotic symptoms caused by medication for Parkinson disease (dopamine agonists)
Adverse Effects: Metabolic effects (usually weight gain, hyperglycemia, dyslipidemia) most prominent Prolonged QT interval Hyperprolactinemia (less pronounced than in FGAs) Neuroleptic malignant syndrome Clozapine can cause agranulocytosis, and lowers the seizure threshold Myocarditis Cardiomyopathy Sinus tachycardia Sedation, somnolence EPS less common Anticholinergic and sympatholytic effect
Monitoring guidelines –> fasting glucose and lipids, blood pressure and waist circumference
Olanzapine
Second-generation antipsychotics (SGAs)
Mechanism:
D2 receptor antagonism (less pronounced than that of FGAs)
5-HT2A receptor antagonism
Interaction with several other receptors (i.e., D3, D4, α-adrenergic, and H1 receptors)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Postpartum psychosis MDD with psychotic features OCD (concomitant medication) Tourette syndrome Anxiety disorders Huntington disease
Adverse Effects: Metabolic effects (usually weight gain, hyperglycemia, dyslipidemia) most prominent Prolonged QT interval Hyperprolactinemia (less pronounced than in FGAs) Neuroleptic malignant syndrome Sedation, somnolence EPS less common Anticholinergic and sympatholytic effect Asymptomatic increase of liver enzymes.
Monitoring guidelines –> fasting glucose and lipids, blood pressure and waist circumference
Risperidone
Second-generation antipsychotics (SGAs)
Mechanism:
D2 receptor antagonism (less pronounced than that of FGAs)
5-HT2A receptor antagonism
Interaction with several other receptors (i.e., D3, D4, α-adrenergic, and H1 receptors)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Postpartum psychosis MDD with psychotic features OCD (concomitant medication) Tourette syndrome Anxiety disorders Huntington disease Acute therapy for dementia (should be reserved for severe symptoms only)
Adverse Effects: Metabolic effects (usually weight gain, hyperglycemia, dyslipidemia) most prominent Prolonged QT interval Hyperprolactinemia (less pronounced than in FGAs) Neuroleptic malignant syndrome Sedation, somnolence EPS less common Anticholinergic and sympatholytic effect
Monitoring guidelines –> fasting glucose and lipids, blood pressure and waist circumference
Quetiapine
Second-generation antipsychotics (SGAs)
Mechanism:
D2 receptor antagonism (less pronounced than that of FGAs)
5-HT2A receptor antagonism
Interaction with several other receptors (i.e., D3, D4, α-adrenergic, and H1 receptors)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Postpartum psychosis MDD with psychotic features OCD (concomitant medication) Tourette syndrome Anxiety disorders Huntington disease
Adverse Effects: Metabolic effects (usually weight gain, hyperglycemia, dyslipidemia) most prominent Prolonged QT interval Hyperprolactinemia (less pronounced than in FGAs) Neuroleptic malignant syndrome Sedation, somnolence EPS less common Anticholinergic and sympatholytic effect
Monitoring guidelines –> fasting glucose and lipids, blood pressure and waist circumference
Amisulpride
Second-generation antipsychotics (SGAs)
Mechanism:
D2 receptor antagonism (less pronounced than that of FGAs)
5-HT2A receptor antagonism
Interaction with several other receptors (i.e., D3, D4, α-adrenergic, and H1 receptors)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Postpartum psychosis MDD with psychotic features OCD (concomitant medication) Tourette syndrome Anxiety disorders Huntington disease
Adverse Effects: Metabolic effects (usually weight gain, hyperglycemia, dyslipidemia) most prominent Prolonged QT interval Hyperprolactinemia (less pronounced than in FGAs) Neuroleptic malignant syndrome Sedation, somnolence EPS less common Anticholinergic and sympatholytic effect
Monitoring guidelines –> fasting glucose and lipids, blood pressure and waist circumference
Ziprasidone
Second-generation antipsychotics (SGAs)
Mechanism:
D2 receptor antagonism (less pronounced than that of FGAs)
5-HT2A receptor antagonism
Interaction with several other receptors (i.e., D3, D4, α-adrenergic, and H1 receptors)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Postpartum psychosis MDD with psychotic features OCD (concomitant medication) Tourette syndrome Anxiety disorders Huntington disease
Adverse Effects: Metabolic effects (usually weight gain, hyperglycemia, dyslipidemia) most prominent Prolonged QT interval Hyperprolactinemia (less pronounced than in FGAs) Neuroleptic malignant syndrome Sedation, somnolence EPS less common Anticholinergic and sympatholytic effect
Monitoring guidelines –> fasting glucose and lipids, blood pressure and waist circumference
Aripiprazole
Second-generation antipsychotics (SGAs)
Mechanism:
Aripiprazole is a partial D2 agonist
5-HT2A receptor antagonism
Interaction with several other receptors (i.e., D3, D4, α-adrenergic, and H1 receptors)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Postpartum psychosis MDD with psychotic features OCD (concomitant medication) Tourette syndrome Anxiety disorders Huntington disease
Adverse Effects: Metabolic effects (usually weight gain, hyperglycemia, dyslipidemia) most prominent Prolonged QT interval Hyperprolactinemia (less pronounced than in FGAs) Neuroleptic malignant syndrome Sedation, somnolence EPS less common Anticholinergic and sympatholytic effect
Monitoring guidelines –> fasting glucose and lipids, blood pressure and waist circumference
Lurasidone
Second-generation antipsychotics (SGAs)
Mechanism:
D2 receptor antagonism (less pronounced than that of FGAs)
5-HT2A receptor antagonism
Interaction with several other receptors (i.e., D3, D4, α-adrenergic, and H1 receptors)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Postpartum psychosis MDD with psychotic features OCD (concomitant medication) Tourette syndrome Anxiety disorders Huntington disease
Adverse Effects: Metabolic effects (usually weight gain, hyperglycemia, dyslipidemia) most prominent Prolonged QT interval Hyperprolactinemia (less pronounced than in FGAs) Neuroleptic malignant syndrome Sedation, somnolence EPS less common Anticholinergic and sympatholytic effect
Monitoring guidelines –> fasting glucose and lipids, blood pressure and waist circumference
Asenapine
Second-generation antipsychotics (SGAs)
Mechanism:
D2 receptor antagonism (less pronounced than that of FGAs)
5-HT2A receptor antagonism
Interaction with several other receptors (i.e., D3, D4, α-adrenergic, and H1 receptors)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Postpartum psychosis MDD with psychotic features OCD (concomitant medication) Tourette syndrome Anxiety disorders Huntington disease
Adverse Effects: Metabolic effects (usually weight gain, hyperglycemia, dyslipidemia) most prominent Prolonged QT interval Hyperprolactinemia (less pronounced than in FGAs) Neuroleptic malignant syndrome Sedation, somnolence EPS less common Anticholinergic and sympatholytic effect
Monitoring guidelines –> fasting glucose and lipids, blood pressure and waist circumference
Iloperidone
Second-generation antipsychotics (SGAs)
Mechanism:
D2 receptor antagonism (less pronounced than that of FGAs)
5-HT2A receptor antagonism
Interaction with several other receptors (i.e., D3, D4, α-adrenergic, and H1 receptors)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Postpartum psychosis MDD with psychotic features OCD (concomitant medication) Tourette syndrome Anxiety disorders Huntington disease
Adverse Effects: Metabolic effects (usually weight gain, hyperglycemia, dyslipidemia) most prominent Prolonged QT interval Hyperprolactinemia (less pronounced than in FGAs) Neuroleptic malignant syndrome Sedation, somnolence EPS less common Anticholinergic and sympatholytic effect
Monitoring guidelines –> fasting glucose and lipids, blood pressure and waist circumference
Paliperidone
Second-generation antipsychotics (SGAs)
Mechanism:
D2 receptor antagonism (less pronounced than that of FGAs)
5-HT2A receptor antagonism
Interaction with several other receptors (i.e., D3, D4, α-adrenergic, and H1 receptors)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Postpartum psychosis MDD with psychotic features OCD (concomitant medication) Tourette syndrome Anxiety disorders Huntington disease
Adverse Effects: Metabolic effects (usually weight gain, hyperglycemia, dyslipidemia) most prominent Prolonged QT interval Hyperprolactinemia (less pronounced than in FGAs) Neuroleptic malignant syndrome Sedation, somnolence EPS less common Anticholinergic and sympatholytic effect
Monitoring guidelines –> fasting glucose and lipids, blood pressure and waist circumference
Tiapride
First-generation antipsychotic drug (although it is sometimes classified as an SGA drug without antipsychotic effects)
Mainly used for tic disorders and Huntington disease
Lithium
Mechanism:
Not established; possibly related to inhibition of phosphoinositol cascade.
Steady state is usually reached 4–5 days after initiation or a change in dosage
95% of lithium is excreted by the kidneys. The remaining part is excreted via sweat and feces.
It is freely filtered at the glomerulus and mostly reabsorbed in the proximal convoluted tubule via sodium channels.
Clinical Use:
First-line therapy for bipolar disorder
Treats acute manic episodes and prevents relapse.
Maintenance therapy
Augmentation in treatment-resistant depression (lithium monotherapy or augmentation (with an antidepressant) is effective in preventing suicide in individuals with unipolar depression and suicidal ideation)
Adverse Effects:
Adverse effects occur at therapeutic levels (0.4–1.0 mEq/L) but tend to be more severe at peak serum concentration of the drug.
Nausea, diarrhea
Weight gain (due to dysregulation of appetite in the hypothalamus)
Dry oral mucosa
Leukocytosis
Nonprogessive, symmetric, fine postural tremor in the distal ends of upper extremities. Often decreases spontaneously over time. Treat with beta blockers (e.g., propranolol) if persistent or severe
Muscle weakness
Acne
Worsening psoriasis
Hair thinning
T-wave depressions (most common), U waves, repolarization abnormalities
Sinus node dysfunction (most commonly sinus bradycardia)
Hypothyroidism
Hyperparathyroidism causing hypercalcemia
Goiter (particularly in second and third trimester of pregnancy)
Nephrogenic diabetes insipidus (lithium interferes with ADH signaling → ↓ aquaporins (water channels) on the collecting duct cell’s surface → ↓ water molecules are reabsorbed and kidneys are unable to concentrate urine → ↑ free water excretion) (polyuria, nocturia, and polydipsia → ↑ risk of dehydration and subsequent lithium toxicity) Treat with amiloride (blocks ENaC channels, reducing urine volume and lithium uptake in the kidneys)
Chronic interstitial nephritis (lithium-associated nephropathy) → interstitial fibrosis, focal nephron atrophy, tubular cysts with chronic use. Risk correlates with the cumulative dose and duration of lithium use. Often occurs in the setting of nephrogenic DI. Can progress to chronic kidney disease
Ebstein anomaly
Thiazides (and other nephrotoxic agents) are implicated in lithium toxicity.
LiTHIUM: Low Thyroid (hypothyroidism) Heart (Ebstein anomaly) Insipidus (nephrogenic diabetes insipidus) Unwanted Movements (tremor)
Absolute contraindications:
Advanced renal failure (creatinine clearance < 30 mL/min)
Severe cardiovascular disease
Relative contraindications:
Concurrent diuretic use
Dehydration, sodium depletion
First trimester of pregnancy if lithium is needed during pregnancy, aim for the minimum effective dose and monitor serum levels regularly.
Monitoring guidelines –> BUN, creatinine and thyroid function
Long-term treatment reduce the risk of suicide attempts and deaths.
Lithium Toxicity
Occurs at serum levels > 1.5 mEq/L.
Causes
Increase in dosage (lithium has a narrow therapeutic window)
Renal impairment from any cause
Low effective circulating volume (e.g., due to dehydration, loop diuretic use, cirrhosis, congestive heart failure)
Medications that can precipitate lithium toxicity by increasing renal absorption of lithium:
- Thiazide diuretics
- NSAIDs (except aspirin)
- ACE inhibitors
- Tetracyclines
- Cyclosporines
Clinical Features:
Gastrointestinal symptoms dominate in acute poisoning. Neuromuscular symptoms may develop as the intoxication progresses.
Nausea, vomiting, and diarrhea (further fluid loss may exacerbate lithium toxicity)
Altered mental status, confusion
Somnolence, coma
Delirium, encephalopathy, psychomotor impairment
Coarse tremors, seizures, fasciculations, myoclonic jerks,
Ataxia, slurred speech, nystagmus
Hyperreflexia
Acute renal failure
Treatment:
Discontinuation of lithium
Hydration with isotonic fluid (0.9% NaCl solution) and electrolyte correction to promote lithium clearance
Hemodialysis is the first-line treatment for severe lithium toxicity
Buspirone
Mechanism:
Stimulates 5-HT1A receptors
Clinical Use:
Generalized anxiety disorder.
Does not cause sedation, addiction, or tolerance.
Takes 1–2 weeks to take effect.
Does not interact with alcohol (vs barbiturates, benzodiazepines).
SSRIs
Fluoxetine, fluvoxamine, paroxetine, sertraline, escitalopram, citalopram.
Mechanism:
Inhibition of serotonin reuptake in synaptic cleft → ↑ serotonin levels in cortico-amygdala pathways
It normally takes 4–8 weeks for antidepressants to have an effect.
Clinical Use: Major depressive disorder (first-line therapy) Generalized anxiety disorder (GAD) Obsessive-compulsive disorder (OCD) Post-traumatic stress disorder (PTSD) Panic disorder Premature ejaculation Premenstrual dysphoric disorder Binge-eating disorder Bulimia nervosa Social anxiety disorder Gambling disorder Somatic symptom disorder Irritable bowel syndrome
Adverse Effects:
Fewer than TCAs.
Sexual dysfunction (e.g., anorgasmia, ↓ libido, erectile or ejaculatory dysfunction)
Diarrhea, nausea, vomiting (because serotonin receptors are located in the area postrema, the stimulation of which causes nausea and vomiting)
Agitation
Insomnia
SIADH
Headache
Increased risk of serotonin syndrome if used concomitantly with other serotonergic drugs (e.g., MAOIs, linezolid, St. John’s wort, dextromethorphan, meperidine, methylene blue)
In the first trimester of pregnancy, paroxetine increases the risk of fetal cardiovascular malformations; in the third trimester, it increases the risk of pulmonary hypertension in the fetus.
Fluoxetine
SSRIs
Mechanism:
Inhibition of serotonin reuptake in synaptic cleft → ↑ serotonin levels in cortico-amygdala pathways
It normally takes 4–8 weeks for antidepressants to have an effect.
Clinical Use: Major depressive disorder (first-line therapy) Generalized anxiety disorder (GAD) Obsessive-compulsive disorder (OCD) Post-traumatic stress disorder (PTSD) Panic disorder Premature ejaculation Premenstrual dysphoric disorder Binge-eating disorder Bulimia nervosa Social anxiety disorder Gambling disorder Somatic symptom disorder Irritable bowel syndrome
Adverse Effects:
Fewer than TCAs.
Sexual dysfunction (e.g., anorgasmia, ↓ libido, erectile or ejaculatory dysfunction)
Diarrhea, nausea, vomiting (because serotonin receptors are located in the area postrema, the stimulation of which causes nausea and vomiting)
Agitation
Insomnia
SIADH
Headache
Increased risk of serotonin syndrome if used concomitantly with other serotonergic drugs (e.g., MAOIs, linezolid, St. John’s wort, dextromethorphan, meperidine, methylene blue)
Paroxetine
SSRIs
Mechanism:
Inhibition of serotonin reuptake in synaptic cleft → ↑ serotonin levels in cortico-amygdala pathways
It normally takes 4–8 weeks for antidepressants to have an effect.
Clinical Use: Major depressive disorder (first-line therapy) Generalized anxiety disorder (GAD) Obsessive-compulsive disorder (OCD) Post-traumatic stress disorder (PTSD) Panic disorder Premature ejaculation Premenstrual dysphoric disorder Binge-eating disorder Bulimia nervosa Social anxiety disorder Gambling disorder Somatic symptom disorder Irritable bowel syndrome
Adverse Effects:
Fewer than TCAs.
Sexual dysfunction (e.g., anorgasmia, ↓ libido, erectile or ejaculatory dysfunction)
Diarrhea, nausea, vomiting (because serotonin receptors are located in the area postrema, the stimulation of which causes nausea and vomiting)
Agitation
Insomnia
SIADH
Headache
Increased risk of serotonin syndrome if used concomitantly with other serotonergic drugs (e.g., MAOIs, linezolid, St. John’s wort, dextromethorphan, meperidine, methylene blue)
In the first trimester of pregnancy, paroxetine increases the risk of fetal cardiovascular malformations; in the third trimester, it increases the risk of pulmonary hypertension in the fetus.
Sertraline
SSRIs
Mechanism:
Inhibition of serotonin reuptake in synaptic cleft → ↑ serotonin levels in cortico-amygdala pathways
It normally takes 4–8 weeks for antidepressants to have an effect.
Clinical Use: Major depressive disorder (first-line therapy) Generalized anxiety disorder (GAD) Obsessive-compulsive disorder (OCD) Post-traumatic stress disorder (PTSD) Panic disorder Premature ejaculation Premenstrual dysphoric disorder Binge-eating disorder Bulimia nervosa Social anxiety disorder Gambling disorder Somatic symptom disorder Irritable bowel syndrome
Adverse Effects:
Fewer than TCAs.
Sexual dysfunction (e.g., anorgasmia, ↓ libido, erectile or ejaculatory dysfunction)
Diarrhea, nausea, vomiting (because serotonin receptors are located in the area postrema, the stimulation of which causes nausea and vomiting)
Agitation
Insomnia
SIADH
Headache
Increased risk of serotonin syndrome if used concomitantly with other serotonergic drugs (e.g., MAOIs, linezolid, St. John’s wort, dextromethorphan, meperidine, methylene blue)
Citalopram
SSRIs
Mechanism:
Inhibition of serotonin reuptake in synaptic cleft → ↑ serotonin levels in cortico-amygdala pathways
It normally takes 4–8 weeks for antidepressants to have an effect.
Clinical Use: Major depressive disorder (first-line therapy) Generalized anxiety disorder (GAD) Obsessive-compulsive disorder (OCD) Post-traumatic stress disorder (PTSD) Panic disorder Premature ejaculation Premenstrual dysphoric disorder Binge-eating disorder Bulimia nervosa Social anxiety disorder Gambling disorder Somatic symptom disorder Irritable bowel syndrome
Adverse Effects:
Fewer than TCAs.
Sexual dysfunction (e.g., anorgasmia, ↓ libido, erectile or ejaculatory dysfunction)
Diarrhea, nausea, vomiting (because serotonin receptors are located in the area postrema, the stimulation of which causes nausea and vomiting)
Agitation
Insomnia
SIADH
Headache
Increased risk of serotonin syndrome if used concomitantly with other serotonergic drugs (e.g., MAOIs, linezolid, St. John’s wort, dextromethorphan, meperidine, methylene blue)
Escitalopram
SSRIs
Mechanism:
Inhibition of serotonin reuptake in synaptic cleft → ↑ serotonin levels in cortico-amygdala pathways
It normally takes 4–8 weeks for antidepressants to have an effect.
Clinical Use: Major depressive disorder (first-line therapy) Generalized anxiety disorder (GAD) Obsessive-compulsive disorder (OCD) Post-traumatic stress disorder (PTSD) Panic disorder Premature ejaculation Premenstrual dysphoric disorder Binge-eating disorder Bulimia nervosa Social anxiety disorder Gambling disorder Somatic symptom disorder Irritable bowel syndrome
Adverse Effects:
Fewer than TCAs.
Sexual dysfunction (e.g., anorgasmia, ↓ libido, erectile or ejaculatory dysfunction)
Diarrhea, nausea, vomiting (because serotonin receptors are located in the area postrema, the stimulation of which causes nausea and vomiting)
Agitation
Insomnia
SIADH
Headache
Increased risk of serotonin syndrome if used concomitantly with other serotonergic drugs (e.g., MAOIs, linezolid, St. John’s wort, dextromethorphan, meperidine, methylene blue)
Fluvoxamine
SSRIs
Mechanism:
Inhibition of serotonin reuptake in synaptic cleft → ↑ serotonin levels in cortico-amygdala pathways
It normally takes 4–8 weeks for antidepressants to have an effect.
Clinical Use: Major depressive disorder (first-line therapy) Generalized anxiety disorder (GAD) Obsessive-compulsive disorder (OCD) Post-traumatic stress disorder (PTSD) Panic disorder Premature ejaculation Premenstrual dysphoric disorder Binge-eating disorder Bulimia nervosa Social anxiety disorder Gambling disorder Somatic symptom disorder Irritable bowel syndrome
Adverse Effects:
Fewer than TCAs.
Sexual dysfunction (e.g., anorgasmia, ↓ libido, erectile or ejaculatory dysfunction)
Diarrhea, nausea, vomiting (because serotonin receptors are located in the area postrema, the stimulation of which causes nausea and vomiting)
Agitation
Insomnia
SIADH
Headache
Increased risk of serotonin syndrome if used concomitantly with other serotonergic drugs (e.g., MAOIs, linezolid, St. John’s wort, dextromethorphan, meperidine, methylene blue)
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Venlafaxine, desvenlafaxine, duloxetine, levomilnacipran, milnacipran
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Clinical Use:
Major depressive disorder (second-line therapy)
Generalized anxiety disorder
Neuropathic pain (e.g. diabetic neuropathy)
Fibromyalgia (duloxetine and milnacipran specifically)
Stress incontinence in women (duloxetine)
Social anxiety disorder, OCD, panic disorder, and PTSD (venlafaxine specifically)
Adverse Effects:
Anxiolytic (stimulant) effect
Increased blood pressure (blood pressure should be well-controlled before initiating SNRI therapy)
Insomnia, strange dreams, nightmares
Can increase cholesterol and triglycerides
Nausea
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Venlafaxine
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Clinical Use:
Major depressive disorder (second-line therapy)
Generalized anxiety disorder
Neuropathic pain (e.g. diabetic neuropathy)
Social anxiety disorder, OCD, panic disorder, and PTSD (venlafaxine specifically)
Adverse Effects:
Anxiolytic (stimulant) effect
Increased blood pressure (blood pressure should be well-controlled before initiating SNRI therapy)
Insomnia, strange dreams, nightmares
Can increase cholesterol and triglycerides
Nausea
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Duloxetine
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Clinical Use:
Major depressive disorder (second-line therapy)
Generalized anxiety disorder
Neuropathic pain (e.g. diabetic neuropathy)
Fibromyalgia (duloxetine and milnacipran specifically)
Stress incontinence in women (duloxetine)
Adverse Effects:
Anxiolytic (stimulant) effect
Increased blood pressure (blood pressure should be well-controlled before initiating SNRI therapy)
Insomnia, strange dreams, nightmares
Can increase cholesterol and triglycerides
Nausea
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Desvenlafaxine
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Clinical Use:
Major depressive disorder (second-line therapy)
Generalized anxiety disorder
Neuropathic pain (e.g. diabetic neuropathy)
Adverse Effects:
Anxiolytic (stimulant) effect
Increased blood pressure (blood pressure should be well-controlled before initiating SNRI therapy)
Insomnia, strange dreams, nightmares
Can increase cholesterol and triglycerides
Nausea
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Levomilnacipran
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Clinical Use:
Major depressive disorder (second-line therapy)
Generalized anxiety disorder
Neuropathic pain (e.g. diabetic neuropathy)
Adverse Effects:
Anxiolytic (stimulant) effect
Increased blood pressure (blood pressure should be well-controlled before initiating SNRI therapy)
Insomnia, strange dreams, nightmares
Can increase cholesterol and triglycerides
Nausea
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Milnacipran
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Clinical Use:
Major depressive disorder (second-line therapy)
Generalized anxiety disorder
Neuropathic pain (e.g. diabetic neuropathy)
Fibromyalgia (duloxetine and milnacipran specifically)
Adverse Effects:
Anxiolytic (stimulant) effect
Increased blood pressure (blood pressure should be well-controlled before initiating SNRI therapy)
Insomnia, strange dreams, nightmares
Can increase cholesterol and triglycerides
Nausea
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Tricyclic Antidepressants
Secondary amines (nortriptyline, desipramine, protriptyline, amoxapine) Tertiary amines (amitriptyline, clomipramine, doxepin, imipramine, trimipramine)
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Secondary amines are more effective than tertiary amines at blocking norepinephrine reuptake
Compared to secondary amines, tertiary amines are more effective at blocking serotonin reuptake and have more anticholinergic effects.
Clinical Use:
Major depressive disorder (third- or fourth-line therapy)
Neuropathic pain (e.g., peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia)
Chronic pain (including fibromyalgia)
Migraine prophylaxis
OCD (clomipramine specifically)
Nocturnal enuresis (limited use due to side effects) (imipramine specifically)
Adverse Effects:
Orthostatic hypotension
Cardiotoxicity due to Na+ channel inhibition in the myocardium (changes in cardiac conductivity velocity, arrhythmias, prolonged QT interval (predisposes to torsades de pointes), wide QRS complex)
Tremor
Respiratory depression
Hyperpyrexia
Anticholinergic symptoms due to blockage of muscarinic cholinergic receptors (more common with tertiary amines)
Tachycardia, arrhythmia (including ventricular fibrillation), hypotension
Confusion, hallucinations, sedation, coma, seizures (confusion and hallucinations are most commonly seen in older patients)
Intestinal ileus, constipation
Urinary retention
Xerostomia, mydriasis, hyperthermia, dry skin
Certain TCAs (e.g., clomipramine) are associated with hyperprolactinemia.
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Risk of anticholinergic toxicity
Contraindications:
Tertiary amines should be avoided in the elderly because of their side-effect profile; Secondary amines (e.g., nortriptyline) are less likely to cause anticholinergic side effects.
Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal)
Prevention of arrhythmia → NaHCO3
3° Tricyclic Antidepressants
Amitriptyline Clomipramine Doxepin Imipramine Trimipramine
2° Tricyclic Antidepressants
Nortriptyline
Desipramine
Protriptyline
Amoxapine
Amitriptyline
3° Tricyclic Antidepressant
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Secondary amines are more effective than tertiary amines at blocking norepinephrine reuptake
Compared to secondary amines, tertiary amines are more effective at blocking serotonin reuptake and have more anticholinergic effects.
Clinical Use:
Major depressive disorder (third- or fourth-line therapy)
Neuropathic pain (e.g., peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia)
Chronic pain (including fibromyalgia)
Migraine prophylaxis
Adverse Effects:
Orthostatic hypotension
Cardiotoxicity due to Na+ channel inhibition in the myocardium (changes in cardiac conductivity velocity, arrhythmias, prolonged QT interval (predisposes to torsades de pointes), wide QRS complex)
Tremor
Respiratory depression
Hyperpyrexia
Anticholinergic symptoms due to blockage of muscarinic cholinergic receptors (more common with tertiary amines)
Tachycardia, arrhythmia (including ventricular fibrillation), hypotension
Confusion, hallucinations, sedation, coma, seizures (confusion and hallucinations are most commonly seen in older patients)
Intestinal ileus, constipation
Urinary retention
Xerostomia, mydriasis, hyperthermia, dry skin
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Risk of anticholinergic toxicity
Contraindications:
Tertiary amines should be avoided in the elderly because of their side-effect profile; Secondary amines (e.g., nortriptyline) are less likely to cause anticholinergic side effects.
Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal)
Prevention of arrhythmia → NaHCO3
Clomipramine
3° Tricyclic Antidepressant
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Secondary amines are more effective than tertiary amines at blocking norepinephrine reuptake
Compared to secondary amines, tertiary amines are more effective at blocking serotonin reuptake and have more anticholinergic effects.
Clinical Use:
Major depressive disorder (third- or fourth-line therapy)
Neuropathic pain (e.g., peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia)
Chronic pain (including fibromyalgia)
Migraine prophylaxis
OCD (clomipramine specifically)
Adverse Effects:
Orthostatic hypotension
Cardiotoxicity due to Na+ channel inhibition in the myocardium (changes in cardiac conductivity velocity, arrhythmias, prolonged QT interval (predisposes to torsades de pointes), wide QRS complex)
Tremor
Respiratory depression
Hyperpyrexia
Anticholinergic symptoms due to blockage of muscarinic cholinergic receptors (more common with tertiary amines)
Tachycardia, arrhythmia (including ventricular fibrillation), hypotension
Confusion, hallucinations, sedation, coma, seizures (confusion and hallucinations are most commonly seen in older patients)
Intestinal ileus, constipation
Urinary retention
Xerostomia, mydriasis, hyperthermia, dry skin
Certain TCAs (e.g., clomipramine) are associated with hyperprolactinemia.
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Risk of anticholinergic toxicity
Contraindications:
Tertiary amines should be avoided in the elderly because of their side-effect profile; Secondary amines (e.g., nortriptyline) are less likely to cause anticholinergic side effects.
Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal)
Prevention of arrhythmia → NaHCO3
Doxepin
3° Tricyclic Antidepressant
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Secondary amines are more effective than tertiary amines at blocking norepinephrine reuptake
Compared to secondary amines, tertiary amines are more effective at blocking serotonin reuptake and have more anticholinergic effects.
Clinical Use:
Major depressive disorder (third- or fourth-line therapy)
Neuropathic pain (e.g., peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia)
Chronic pain (including fibromyalgia)
Migraine prophylaxis
Adverse Effects:
Orthostatic hypotension
Cardiotoxicity due to Na+ channel inhibition in the myocardium (changes in cardiac conductivity velocity, arrhythmias, prolonged QT interval (predisposes to torsades de pointes), wide QRS complex)
Tremor
Respiratory depression
Hyperpyrexia
Anticholinergic symptoms due to blockage of muscarinic cholinergic receptors (more common with tertiary amines)
Tachycardia, arrhythmia (including ventricular fibrillation), hypotension
Confusion, hallucinations, sedation, coma, seizures (confusion and hallucinations are most commonly seen in older patients)
Intestinal ileus, constipation
Urinary retention
Xerostomia, mydriasis, hyperthermia, dry skin
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Risk of anticholinergic toxicity
Contraindications:
Tertiary amines should be avoided in the elderly because of their side-effect profile; Secondary amines (e.g., nortriptyline) are less likely to cause anticholinergic side effects.
Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal)
Prevention of arrhythmia → NaHCO3
Imipramine
3° Tricyclic Antidepressant
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Secondary amines are more effective than tertiary amines at blocking norepinephrine reuptake
Compared to secondary amines, tertiary amines are more effective at blocking serotonin reuptake and have more anticholinergic effects.
Clinical Use:
Major depressive disorder (third- or fourth-line therapy)
Neuropathic pain (e.g., peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia)
Chronic pain (including fibromyalgia)
Migraine prophylaxis
Nocturnal enuresis (limited use due to side effects)(imipramine specifically)
Adverse Effects:
Orthostatic hypotension
Cardiotoxicity due to Na+ channel inhibition in the myocardium (changes in cardiac conductivity velocity, arrhythmias, prolonged QT interval (predisposes to torsades de pointes), wide QRS complex)
Tremor
Respiratory depression
Hyperpyrexia
Anticholinergic symptoms due to blockage of muscarinic cholinergic receptors (more common with tertiary amines)
Tachycardia, arrhythmia (including ventricular fibrillation), hypotension
Confusion, hallucinations, sedation, coma, seizures (confusion and hallucinations are most commonly seen in older patients)
Intestinal ileus, constipation
Urinary retention
Xerostomia, mydriasis, hyperthermia, dry skin
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Risk of anticholinergic toxicity
Contraindications:
Tertiary amines should be avoided in the elderly because of their side-effect profile; Secondary amines (e.g., nortriptyline) are less likely to cause anticholinergic side effects.
Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal)
Prevention of arrhythmia → NaHCO3
Trimipramine
3° Tricyclic Antidepressant
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Secondary amines are more effective than tertiary amines at blocking norepinephrine reuptake
Compared to secondary amines, tertiary amines are more effective at blocking serotonin reuptake and have more anticholinergic effects.
Clinical Use:
Major depressive disorder (third- or fourth-line therapy)
Neuropathic pain (e.g., peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia)
Chronic pain (including fibromyalgia)
Migraine prophylaxis
Adverse Effects:
Orthostatic hypotension
Cardiotoxicity due to Na+ channel inhibition in the myocardium (changes in cardiac conductivity velocity, arrhythmias, prolonged QT interval (predisposes to torsades de pointes), wide QRS complex)
Tremor
Respiratory depression
Hyperpyrexia
Anticholinergic symptoms due to blockage of muscarinic cholinergic receptors (more common with tertiary amines)
Tachycardia, arrhythmia (including ventricular fibrillation), hypotension
Confusion, hallucinations, sedation, coma, seizures (confusion and hallucinations are most commonly seen in older patients)
Intestinal ileus, constipation
Urinary retention
Xerostomia, mydriasis, hyperthermia, dry skin
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Risk of anticholinergic toxicity
Contraindications:
Tertiary amines should be avoided in the elderly because of their side-effect profile; Secondary amines (e.g., nortriptyline) are less likely to cause anticholinergic side effects.
Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal)
Prevention of arrhythmia → NaHCO3
Nortriptyline
2° Tricyclic Antidepressant
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Secondary amines are more effective than tertiary amines at blocking norepinephrine reuptake
Compared to secondary amines, tertiary amines are more effective at blocking serotonin reuptake and have more anticholinergic effects.
Clinical Use:
Major depressive disorder (third- or fourth-line therapy)
Neuropathic pain (e.g., peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia)
Chronic pain (including fibromyalgia)
Migraine prophylaxis
Adverse Effects:
Orthostatic hypotension
Cardiotoxicity due to Na+ channel inhibition in the myocardium (changes in cardiac conductivity velocity, arrhythmias, prolonged QT interval (predisposes to torsades de pointes), wide QRS complex)
Tremor
Respiratory depression
Hyperpyrexia
Anticholinergic symptoms due to blockage of muscarinic cholinergic receptors (more common with tertiary amines)
Tachycardia, arrhythmia (including ventricular fibrillation), hypotension
Confusion, hallucinations, sedation, coma, seizures (confusion and hallucinations are most commonly seen in older patients)
Intestinal ileus, constipation
Urinary retention
Xerostomia, mydriasis, hyperthermia, dry skin
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Risk of anticholinergic toxicity
Contraindications:
Tertiary amines should be avoided in the elderly because of their side-effect profile; Secondary amines (e.g., nortriptyline) are less likely to cause anticholinergic side effects.
Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal)
Prevention of arrhythmia → NaHCO3
Desipramine
2° Tricyclic Antidepressant
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Secondary amines are more effective than tertiary amines at blocking norepinephrine reuptake
Compared to secondary amines, tertiary amines are more effective at blocking serotonin reuptake and have more anticholinergic effects.
Clinical Use:
Major depressive disorder (third- or fourth-line therapy)
Neuropathic pain (e.g., peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia)
Chronic pain (including fibromyalgia)
Migraine prophylaxis
Adverse Effects:
Orthostatic hypotension
Cardiotoxicity due to Na+ channel inhibition in the myocardium (changes in cardiac conductivity velocity, arrhythmias, prolonged QT interval (predisposes to torsades de pointes), wide QRS complex)
Tremor
Respiratory depression
Hyperpyrexia
Anticholinergic symptoms due to blockage of muscarinic cholinergic receptors (more common with tertiary amines)
Tachycardia, arrhythmia (including ventricular fibrillation), hypotension
Confusion, hallucinations, sedation, coma, seizures (confusion and hallucinations are most commonly seen in older patients)
Intestinal ileus, constipation
Urinary retention
Xerostomia, mydriasis, hyperthermia, dry skin
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Risk of anticholinergic toxicity
Contraindications:
Tertiary amines should be avoided in the elderly because of their side-effect profile; Secondary amines (e.g., nortriptyline) are less likely to cause anticholinergic side effects.
Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal)
Prevention of arrhythmia → NaHCO3
Protriptyline
2° Tricyclic Antidepressant
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Secondary amines are more effective than tertiary amines at blocking norepinephrine reuptake
Compared to secondary amines, tertiary amines are more effective at blocking serotonin reuptake and have more anticholinergic effects.
Clinical Use:
Major depressive disorder (third- or fourth-line therapy)
Neuropathic pain (e.g., peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia)
Chronic pain (including fibromyalgia)
Migraine prophylaxis
Adverse Effects:
Orthostatic hypotension
Cardiotoxicity due to Na+ channel inhibition in the myocardium (changes in cardiac conductivity velocity, arrhythmias, prolonged QT interval (predisposes to torsades de pointes), wide QRS complex)
Tremor
Respiratory depression
Hyperpyrexia
Anticholinergic symptoms due to blockage of muscarinic cholinergic receptors (more common with tertiary amines)
Tachycardia, arrhythmia (including ventricular fibrillation), hypotension
Confusion, hallucinations, sedation, coma, seizures (confusion and hallucinations are most commonly seen in older patients)
Intestinal ileus, constipation
Urinary retention
Xerostomia, mydriasis, hyperthermia, dry skin
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Risk of anticholinergic toxicity
Contraindications:
Tertiary amines should be avoided in the elderly because of their side-effect profile; Secondary amines (e.g., nortriptyline) are less likely to cause anticholinergic side effects.
Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal)
Prevention of arrhythmia → NaHCO3
Amoxapine
2° Tricyclic Antidepressant
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Secondary amines are more effective than tertiary amines at blocking norepinephrine reuptake
Compared to secondary amines, tertiary amines are more effective at blocking serotonin reuptake and have more anticholinergic effects.
Clinical Use:
Major depressive disorder (third- or fourth-line therapy)
Neuropathic pain (e.g., peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia)
Chronic pain (including fibromyalgia)
Migraine prophylaxis
Adverse Effects:
Orthostatic hypotension
Cardiotoxicity due to Na+ channel inhibition in the myocardium (changes in cardiac conductivity velocity, arrhythmias, prolonged QT interval (predisposes to torsades de pointes), wide QRS complex)
Tremor
Respiratory depression
Hyperpyrexia
Anticholinergic symptoms due to blockage of muscarinic cholinergic receptors (more common with tertiary amines)
Tachycardia, arrhythmia (including ventricular fibrillation), hypotension
Confusion, hallucinations, sedation, coma, seizures (confusion and hallucinations are most commonly seen in older patients)
Intestinal ileus, constipation
Urinary retention
Xerostomia, mydriasis, hyperthermia, dry skin
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Risk of anticholinergic toxicity
Contraindications:
Tertiary amines should be avoided in the elderly because of their side-effect profile; Secondary amines (e.g., nortriptyline) are less likely to cause anticholinergic side effects.
Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal)
Prevention of arrhythmia → NaHCO3
Monoamine oxidase inhibitors
Tranylcypromine, Phenelzine, Isocarboxazid, Selegiline (selective MAO-B inhibitor).
Mechanism:
Nonselective inhibition of monoamine oxidase → ↓ breakdown of epinephrine, norepinephrine, serotonin, and dopamine → ↑ levels of epinephrine, norepinephrine, serotonin, and dopamine
Selegiline → selective MAO-B inhibitor → mainly ↓ breakdown of dopamine → ↑ levels of dopamine
Clincial Use:
Major depressive disorder (third- or fourth-line therapy) particularly effective treatment for atypical depression
Parkinson disease → selegiline (as an adjunct to carbidopa-levodopa)
Anxiety
Adverse Effects:
CNS stimulation
Sexual dysfunction
Orthostatic hypotension
Weight gain
Hypertensive crisis with ingestion of foods containing tyramine (ex, aged cheeses, smoked/cured meats, alcoholic beverages (especially beer and red wine), dried fruits, fava beans, chocolate). Tyramine stimulates the sympathetic nervous system by releasing other neurotransmitters, such as noradrenaline, from vesicles into the synaptic cleft.
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs, including linezolid, SSRIs, TCAs, meperidine, dextromethorphan, and St. John’s wort
Before starting new serotonergic drugs or ceasing dietary restrictions (e.g., foods containing tyramine), MAOI therapy has to be stopped for at least 2 weeks.
Rarely used due to poor side-effect profile
For the treatment of depression, selegiline is available as a transdermal patch (the oral form is only used for Parkinson disease).
Tranylcypromine
Monoamine oxidase inhibitor
Mechanism:
Nonselective inhibition of monoamine oxidase → ↓ breakdown of epinephrine, norepinephrine, serotonin, and dopamine → ↑ levels of epinephrine, norepinephrine, serotonin, and dopamine
Clincial Use:
Major depressive disorder (third- or fourth-line therapy) particularly effective treatment for atypical depression
Anxiety
Adverse Effects:
CNS stimulation
Sexual dysfunction
Orthostatic hypotension
Weight gain
Hypertensive crisis with ingestion of foods containing tyramine (ex, aged cheeses, smoked/cured meats, alcoholic beverages (especially beer and red wine), dried fruits, fava beans, chocolate). Tyramine stimulates the sympathetic nervous system by releasing other neurotransmitters, such as noradrenaline, from vesicles into the synaptic cleft.
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs, including linezolid, SSRIs, TCAs, meperidine, dextromethorphan, and St. John’s wort
Before starting new serotonergic drugs or ceasing dietary restrictions (e.g., foods containing tyramine), MAOI therapy has to be stopped for at least 2 weeks.
Rarely used due to poor side-effect profile
Phenelzine
Monoamine oxidase inhibitor
Mechanism:
Nonselective inhibition of monoamine oxidase → ↓ breakdown of epinephrine, norepinephrine, serotonin, and dopamine → ↑ levels of epinephrine, norepinephrine, serotonin, and dopamine
Clincial Use:
Major depressive disorder (third- or fourth-line therapy) particularly effective treatment for atypical depression
Anxiety
Adverse Effects:
- CNS stimulation
- Sexual dysfunction
- Orthostatic hypotension
- Weight gain
- Hypertensive crisis with ingestion of foods containing tyramine (ex, aged cheeses, smoked/cured meats, alcoholic beverages (especially beer and red wine), dried fruits, fava beans, chocolate). Tyramine stimulates the sympathetic nervous system by releasing other neurotransmitters, such as noradrenaline, from vesicles into the synaptic cleft.
- Risk of serotonin syndrome if used concomitantly with other serotonergic drugs, including linezolid, SSRIs, TCAs, meperidine, dextromethorphan, and St. John’s wort
- Before starting new serotonergic drugs or ceasing dietary restrictions (e.g., foods containing tyramine), MAOI therapy has to be stopped for at least 2 weeks.
- Rarely used due to poor side-effect profile
Selegiline
Monoamine oxidase inhibitor
Mechanism:
Nonselective inhibition of monoamine oxidase → ↓ breakdown of epinephrine, norepinephrine, serotonin, and dopamine → ↑ levels of epinephrine, norepinephrine, serotonin, and dopamine
Selegiline → selective MAO-B inhibitor → mainly ↓ breakdown of dopamine → ↑ levels of dopamine
Clincial Use:
Major depressive disorder (third- or fourth-line therapy) particularly effective treatment for atypical depression
Parkinson disease → selegiline (as an adjunct to carbidopa-levodopa)
Anxiety
Adverse Effects:
CNS stimulation
Sexual dysfunction
Orthostatic hypotension
Weight gain
Hypertensive crisis with ingestion of foods containing tyramine (ex, aged cheeses, smoked/cured meats, alcoholic beverages (especially beer and red wine), dried fruits, fava beans, chocolate). Tyramine stimulates the sympathetic nervous system by releasing other neurotransmitters, such as noradrenaline, from vesicles into the synaptic cleft.
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs, including linezolid, SSRIs, TCAs, meperidine, dextromethorphan, and St. John’s wort
Before starting new serotonergic drugs or ceasing dietary restrictions (e.g., foods containing tyramine), MAOI therapy has to be stopped for at least 2 weeks.
Rarely used due to poor side-effect profile
For the treatment of depression, selegiline is available as a transdermal patch (the oral form is only used for Parkinson disease).
Isocarboxazid
Monoamine oxidase inhibitor
Mechanism:
Nonselective inhibition of monoamine oxidase → ↓ breakdown of epinephrine, norepinephrine, serotonin, and dopamine → ↑ levels of epinephrine, norepinephrine, serotonin, and dopamine
Clincial Use:
Major depressive disorder (third- or fourth-line therapy) particularly effective treatment for atypical depression
Anxiety
Adverse Effects:
CNS stimulation
Sexual dysfunction
Orthostatic hypotension
Weight gain
Hypertensive crisis with ingestion of foods containing tyramine (ex, aged cheeses, smoked/cured meats, alcoholic beverages (especially beer and red wine), dried fruits, fava beans, chocolate). Tyramine stimulates the sympathetic nervous system by releasing other neurotransmitters, such as noradrenaline, from vesicles into the synaptic cleft.
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs, including linezolid, SSRIs, TCAs, meperidine, dextromethorphan, and St. John’s wort
Before starting new serotonergic drugs or ceasing dietary restrictions (e.g., foods containing tyramine), MAOI therapy has to be stopped for at least 2 weeks.
Rarely used due to poor side-effect profile
Trazodone
Atypical Antidepressant
Mechanism:
Block postsynaptic type 2 serotonin receptors (5-HT2)
Weak inhibition of serotonin reuptake → ↑ serotonin levels
Antagonist of H1 and α1-adrenergic receptors
Clinical Use:
Insomnia
Major depressive disorder (high doses required)
Mainly used as an adjunct to other antidepressants for treating insomnia associated with depression
Two-week washout period before starting other serotonergic drugs
Adverse Effects: Priapism Sedation (due to H1 antagonism) Orthostatic hypotension Nausea Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Nefazodone
Atypical Antidepressant
Mechanism:
Block postsynaptic type 2 serotonin receptors (5-HT2)
Weak inhibition of serotonin reuptake → ↑ serotonin levels
Antagonist of H1 and α1-adrenergic receptors
Clinical Use:
Insomnia
Major depressive disorder (high doses required)
Mainly used as an adjunct to other antidepressants for treating insomnia associated with depression
Two-week washout period before starting other serotonergic drugs
Adverse Effects: Priapism Sedation (due to H1 antagonism) Orthostatic hypotension Nausea Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Mirtazapine
Atypical Antidepressant
Mechaism:
Selective α2-adrenergic antagonist → ↑ serotonin and norepinephrine release
5-HT2 and 5-HT3 receptor antagonists → ↑ effect of serotonin on free 5-HT1 receptor is the likely cause of antidepressant action
H1 antagonist
Clinical Use:
Major depressive disorder, especially in patients who are underweight and/or who have insomnia
Adverse Effects:
↑ Appetite and weight gain (can also be a desired effect)
Sedation (due to H1 antagonism) (can also be a desired effect)
↑ Serum cholesterol and triglyceride levels
Minimal sexual side effects
Dry mouth
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Bupropion
Atypical Antidepressant
Mechanism:
Not fully understood, but thought to increase dopamine and norepinephrine levels via reuptake inhibition
Clinical Use:
Smoking cessation (used in conjunction with counseling and nicotine replacement)
Major depressive disorder
Adverse Effects:
Stimulant effect
Tachycardia, palpitations
Weight loss
Neuropsychiatric symptoms (insomnia, agitation, headache)
Reduction of seizure threshold (should be avoided in patients at increased risk for seizure (e.g., history of epilepsy, anorexia/bulimia, alcohol or benzodiazepine withdrawal))
Does not cause sexual side effects
Dry mouth
Rsk of serotonin syndrome if used concomitantly with other serotonergic drugs
Vilazodone
Atypical Antidepressant
Mechanism:
Inhibition of serotonin reuptake in synaptic cleft → ↑ serotonin levels
5-HT1A receptor partial agonist
Clinical Use:
Major depressive disorder
Adverse Effects:
Headaches
Nausea, diarrhea
Sleep disturbances
Sexual dysfunction
Anticholinergic effects (e.g., dry mouth)
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Vortioxetine
Atypical Antidepressant
Mechanism:
Inhibition of serotonin reuptake in synaptic cleft → ↑ serotonin levels
5-HT1A receptor agonist
5-HT3 receptor antagonist
Clinical Use:
Major depressive disorder
Adverse Effects:
Sexual dysfunction
Nausea
Abnormal dreams
Sleep disturbance
Anticholinergic effects (e.g., dry mouth)
Risk of serotonin syndrome if used concomitantly with other serotonergic drugs
Rare cases of pancreatitis have been reported.
Varenicline
Atypical Antidepressant
Mechanism:
Nicotinic ACh receptor partial agonist
Stimulates dopamine activity → decreases nicotine cravings and withdrawal
Clinical Use:
Smoking cessation
Adverse Effects:
Mood disturbances, e.g. suicidal ideation, depression
Sleep disturbances
Seizures
St. John’s Wort
Mechanism:
A flowering plant (Hypericum perforatum) used as a medicinal herb for depression
Over-the-counter availability
Clinical Use:
Although not approved by the FDA, which considers it a dietary supplement, there are some studies that support St. John’s wort is superior to placebo in treating mild depression.
Adverse Effects:
Inducer of cytochrome P450
Serotonin syndrome if taken with drugs that increase serotonin levels
Bexpiprazole
Atypical Antipsychotic
Mechanism:
D2 partial agonist
5-HT2A receptor antagonism
Interaction with several other receptors (i.e., D3, D4, α-adrenergic, and H1 receptors)
Clinical Use: Schizophrenia Bipolar disorder Acute psychosis Postpartum psychosis MDD with psychotic features OCD (concomitant medication) Tourette syndrome Anxiety disorders Huntington disease
Adverse Effects: Metabolic effects (usually weight gain, hyperglycemia, dyslipidemia) most prominent Prolonged QT interval Hyperprolactinemia (less pronounced than in FGAs) Neuroleptic malignant syndrome Sedation, somnolence EPS less common Anticholinergic and sympatholytic effect
Monitoring guidelines –> fasting glucose and lipids, blood pressure and waist circumference
Lisdexamfetamine
Mechanism:
Prodrug of the stimulant dextroamphetamine
Indirect and central sympathomimetic activity → increased release and blocked reuptake of norepinephrine and dopamine (minor effect on serotonin) → increased concentration in the synaptic cleft
Clinical Use:
Binge eating disorder
Attention-deficit/hyperactivity disorder (first-line therapy for patients ≥ 6 years of age)
Narcolepsy
Adverse Effects: Nervousness Agitation Anxiety Insomnia Anorexia Tachycardia Hypertension Weight loss Tics
Adverse sympathomimetic effects (anxiety, agitation, restlessness, bruxism, tics, difficulties falling asleep (insomnia), reduced appetite, nausea, vomiting (causes weight loss), increased arterial blood pressure, tachycardia)
Epileptogenic potential (reduces the threshold for seizures and tics)
Decreased growth rate (reversible if medication is stopped)
Euphoria
Rarely, priapism
Methylphenidate
Mechanism:
Prodrug of the stimulant dextroamphetamine
Indirect and central sympathomimetic activity → increased release and blocked reuptake of norepinephrine and dopamine (minor effect on serotonin) → increased concentration in the synaptic cleft
Clinical Use:
Binge eating disorder
Attention-deficit/hyperactivity disorder (first-line therapy for patients ≥ 6 years of age)
Narcolepsy
Adverse Effects: Nervousness Agitation Anxiety Insomnia Anorexia Tachycardia Hypertension Weight loss Tics
Adverse sympathomimetic effects (anxiety, agitation, restlessness, bruxism, tics, difficulties falling asleep (insomnia), reduced appetite, nausea, vomiting (causes weight loss), increased arterial blood pressure, tachycardia)
Epileptogenic potential (reduces the threshold for seizures and tics)
Decreased growth rate (reversible if medication is stopped)
Euphoria
Rarely, priapism
Dextroamphetamine
Mechanism:
Prodrug of the stimulant dextroamphetamine
Indirect and central sympathomimetic activity → increased release and blocked reuptake of norepinephrine and dopamine (minor effect on serotonin) → increased concentration in the synaptic cleft
Clinical Use:
Binge eating disorder
Attention-deficit/hyperactivity disorder (first-line therapy for patients ≥ 6 years of age)
Narcolepsy
Adverse Effects: Nervousness Agitation Anxiety Insomnia Anorexia Tachycardia Hypertension Weight loss Tics
Adverse sympathomimetic effects (anxiety, agitation, restlessness, bruxism, tics, difficulties falling asleep (insomnia), reduced appetite, nausea, vomiting (causes weight loss), increased arterial blood pressure, tachycardia)
Epileptogenic potential (reduces the threshold for seizures and tics)
Decreased growth rate (reversible if medication is stopped)
Euphoria
Rarely, priapism
Methamphetamine
Mechanism:
Prodrug of the stimulant dextroamphetamine
Indirect and central sympathomimetic activity → increased release and blocked reuptake of norepinephrine and dopamine (minor effect on serotonin) → increased concentration in the synaptic cleft
Clinical Use:
Binge eating disorder
Attention-deficit/hyperactivity disorder (first-line therapy for patients ≥ 6 years of age)
Narcolepsy
Adverse Effects: Nervousness Agitation Anxiety Insomnia Anorexia Tachycardia Hypertension Weight loss Tics
Adverse sympathomimetic effects (anxiety, agitation, restlessness, bruxism, tics, difficulties falling asleep (insomnia), reduced appetite, nausea, vomiting (causes weight loss), increased arterial blood pressure, tachycardia)
Epileptogenic potential (reduces the threshold for seizures and tics)
Decreased growth rate (reversible if medication is stopped)
Euphoria
Rarely, priapism
Atomoxetine
Nonstimulant
Mechanism:
Selective norepinephrine reuptake inhibitor (NRI) that increases the concentration of norepinephrine in the synaptic cleft
Clinical Use:
Second-line therapy for patients with ADHD ≥ 6 years of age
Preferred in patients with substance abuse disorder or in patients in whom stimulant addiction may be a concern. In patients with active substance use disorder, this condition should be treated before initiating therapy for ADHD.
Advantage:
No potential for addiction → not a schedule II prescription drug (normal prescription drug)
Limitations:
Meta-analyses revealed an increased rate of suicidal actions in children and adolescents being treated with atomoxetine.
