ANTIDEPRESSANTS
Tricyclic Antidepressants
Act on neurotransmitters serotonin and norepinephrine by inhibiting their reuptake at the presynaptic
neuron. Also, act on histamine (drowsiness and weight gain) and acetylcholine.
Administered orally, highly lipophilic and protein-bound, long half-life, steady-state five days
First pass by the liver and excreted from kidneys
Contraindicated in-cardiovascular disease (HEART DISEASE), glaucoma, prostatic hypertrophy, or
urinary retention, hypersensitivity, and MAOIs
o Contraindicated in the elderly population (BPH, Glaucoma, Constipation)
o Pregnancy Category C
o Tardive dyskinesia, acute hepatitis, and neuroleptic malignant syndrome (amoxapine)
o Titrate gradually, nausea, headache, vertigo, malaise, and nightmare- abrupt discontinuation
Use caution- DO NOT GIVE significant risk for cardiac conduction disorder/prolonged QRS and
PR/QT interval (baseline ECG), seizure monitoring, monitor for suicidal ideation, caution in elderly
due to anticholinergic and norepinephrine effect (confusion, orthostatic hypotension, and falls)
Adverse effects- (ANTICHOLINERGIC) dry mouth, constipation, urinary hesitancy/retention,
blurred vision, sedation, orthostatic hypotension, weight gain/increased appetite, nausea/weight gain,
gynecomastia, tinnitus, euphoria, mania, change in libido
Uses- Depression, Enuresis. Obsessive-compulsive disorder (clomipramine), Panic disorder
(imipramine), Insomnia (doxepin, amitriptyline, trazodone), Neuropathic pain (amitriptyline,
imipramine)
Take medication at the same time each day; don’t miss any doses, monitor LFTs
Monoamine Oxidase Inhibitors (MAOIs)
Irreversibly inactivating the enzymes that metabolize norepinephrine, serotonin, and dopamine increases these
neurotransmitters' availability. Prevent the breakdown of tyramine. NOT FIRST LINE OF TREATMENT
Major first-pass effect, metabolized by the liver, excreted by the kidneys, Half-life 1 to 3 hours, Effects
immediate/14 days, onset 1 to 2 weeks
Contraindications- liver or kidney disease, hypersensitivity, congestive heart failure, or arteriosclerotic disease
age older than 60 (Not approved in children)
o Not used in patients with impulsive, cognitive impairment, cannot follow dietary constrictions
o Pregnant Category C/excreted from breast milk
Adverse- Insomnia, Anxiety, agitation
o Dry mouth, blurred vision, urinary retention, and constipation (anticholinergic)
o Common- dizziness, headaches, insomnia, restlessness, and hypotension
, Hypertensive Crisis - Avoid food containing tyramine (Wine/cheese/aged/fermented/yogurt sour cream/soy
sauce) and drugs that raise blood pressure (anticholinergics, sympathomimetics, stimulants), AVOID
serotonergic drugs Ex: Imitrex
o Hypertensive crisis- headaches, heart palpitation, stiff/sore neck, chest tightness, tachycardia,
sweating, and dilated pupils (treatment Phentolamine)
Look for neurologic symptoms eye grounds, listen to heart (ekg)
Use- Treat resistant unipolar depression, panic disorder, and atypical depression associated with borderline
personality disorder
Monitor- liver function test
Selective Serotonin Reuptake Inhibitors (SSRIs)
Affects the serotonin neurotransmitter in the synaptic cleft by blocking the serotonin transporter from
returning the remaining serotonin to the presynaptic cell.
o Fluoxetine-affects dopamine
o Citalopram & escitalopram- true SSRIs
Orally, highly protein-bound and variable biodistribution, peak levels range from 1 to 8 hours
Significant first pass, metabolized by the CYP450 system, excreted by the kidneys
Contraindications- Hypersensitivity, MAOI, severe hepatic or renal impairment, avoided in the first and last
trimester of pregnancy
Adverse- Taper over the first week nausea/vomiting, headache, light-headedness, dizziness, dry mouth,
increased sweating, weight gain or loss, exacerbation of anxiety, agitation, sexual side effect
o Serotonin syndrome- (St. John’s wort & S-adenosylmethionine) Nausea, diarrhea, shivering,
sweating, hyperthermia, vasoconstriction, tachycardia, hypertension, myoclonic jerking, tremor,
agitation, ataxia, disorientation, confusion, and delirium
o Withdrawal symptoms- (paroxetine, sertraline, citalopram, escitalopram)- nausea, dizziness,
and paresthesia
o CNS depression- Avoid alcohol, antihistamines, opioid analgesics
Use- Depression, anxiety, panic disorder, OCD, and Bulimia. Premenstrual dysphoric disorder,
posttraumatic stress disorder, generalized anxiety disorder, and social phobia.
o Off-label anorexia, depressive phase of bipolar, chronic headaches, pain
Monitor- mood/suicidal ideations
Can take 2-6 weeks, but usually 3 to 4 weeks for full effect. Start low dose reduce side effects
WEAN MEDICATION SLOWLY, DO NOT ABRUPTLY STOP
, Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
Block the serotonin and norepinephrine transporters by inhibiting the reuptake of norepinephrine
and increasing the availability to bind with the postsynaptic receptors (Venlafaxine, duloxetine,
desvenlafaxine)
Metabolized by the liver, excreted by the urine
Contraindications- monitor for mood stability, Pregnancy category C, avoid pregnancy
Use- Major depression and bipolar mood disorders
o Venlafaxine- anxiety disorder, generalized anxiety disorder, social phobia, PTSD
o Duloxetine- neuropathic pain & overactive bladder
Adverse side effects- Headache, somnolence, dizziness, insomnia, nervousness, dry mouth,
constipation, abnormal ejaculation, anorexia/weight loss, elevated BP
Monitor- Liver function, suicidal risk, tapered off medication if pregnant, especially in the third
trimester, do not stop abruptly (withdrawal syndrome)
Atypical Antidepressants
Weak inhibits of presynaptic uptake of dopamine and norepinephrine. Does not inhibit the reuptake of
serotonin
Rapidly absorbed and bound to protein
Metabolized via CYP2D6,1A2, and 3A, 75% through urine and 15% in feces
Contraindicated in patients with seizures (severe head injury, severe stroke, CNS tumor, CNS
infection), anorexia nervosa or bulimia, withdrawal from alcohol, benzodiazepines, and
barbiturates, hypersensitivity
Adverse- Insomnia, headache, agitation, dizziness, diaphoresis, nausea/vomiting, xerostomia,
constipation
Off-label- Depression, Not indicated for depression and anxiety alone
Use- patients who do not respond well to SSRIs or have weight fain/sexual dysfunction
o Mirtazapine- drowsiness is helpful in patients who have insomnia as a symptom of
depression
o Combined with SSRI can help anxiety and depression, augment SSRIs
Tricyclic Antidepressants
Act on neurotransmitters serotonin and norepinephrine by inhibiting their reuptake at the presynaptic
neuron. Also, act on histamine (drowsiness and weight gain) and acetylcholine.
Administered orally, highly lipophilic and protein-bound, long half-life, steady-state five days
First pass by the liver and excreted from kidneys
Contraindicated in-cardiovascular disease (HEART DISEASE), glaucoma, prostatic hypertrophy, or
urinary retention, hypersensitivity, and MAOIs
o Contraindicated in the elderly population (BPH, Glaucoma, Constipation)
o Pregnancy Category C
o Tardive dyskinesia, acute hepatitis, and neuroleptic malignant syndrome (amoxapine)
o Titrate gradually, nausea, headache, vertigo, malaise, and nightmare- abrupt discontinuation
Use caution- DO NOT GIVE significant risk for cardiac conduction disorder/prolonged QRS and
PR/QT interval (baseline ECG), seizure monitoring, monitor for suicidal ideation, caution in elderly
due to anticholinergic and norepinephrine effect (confusion, orthostatic hypotension, and falls)
Adverse effects- (ANTICHOLINERGIC) dry mouth, constipation, urinary hesitancy/retention,
blurred vision, sedation, orthostatic hypotension, weight gain/increased appetite, nausea/weight gain,
gynecomastia, tinnitus, euphoria, mania, change in libido
Uses- Depression, Enuresis. Obsessive-compulsive disorder (clomipramine), Panic disorder
(imipramine), Insomnia (doxepin, amitriptyline, trazodone), Neuropathic pain (amitriptyline,
imipramine)
Take medication at the same time each day; don’t miss any doses, monitor LFTs
Monoamine Oxidase Inhibitors (MAOIs)
Irreversibly inactivating the enzymes that metabolize norepinephrine, serotonin, and dopamine increases these
neurotransmitters' availability. Prevent the breakdown of tyramine. NOT FIRST LINE OF TREATMENT
Major first-pass effect, metabolized by the liver, excreted by the kidneys, Half-life 1 to 3 hours, Effects
immediate/14 days, onset 1 to 2 weeks
Contraindications- liver or kidney disease, hypersensitivity, congestive heart failure, or arteriosclerotic disease
age older than 60 (Not approved in children)
o Not used in patients with impulsive, cognitive impairment, cannot follow dietary constrictions
o Pregnant Category C/excreted from breast milk
Adverse- Insomnia, Anxiety, agitation
o Dry mouth, blurred vision, urinary retention, and constipation (anticholinergic)
o Common- dizziness, headaches, insomnia, restlessness, and hypotension
, Hypertensive Crisis - Avoid food containing tyramine (Wine/cheese/aged/fermented/yogurt sour cream/soy
sauce) and drugs that raise blood pressure (anticholinergics, sympathomimetics, stimulants), AVOID
serotonergic drugs Ex: Imitrex
o Hypertensive crisis- headaches, heart palpitation, stiff/sore neck, chest tightness, tachycardia,
sweating, and dilated pupils (treatment Phentolamine)
Look for neurologic symptoms eye grounds, listen to heart (ekg)
Use- Treat resistant unipolar depression, panic disorder, and atypical depression associated with borderline
personality disorder
Monitor- liver function test
Selective Serotonin Reuptake Inhibitors (SSRIs)
Affects the serotonin neurotransmitter in the synaptic cleft by blocking the serotonin transporter from
returning the remaining serotonin to the presynaptic cell.
o Fluoxetine-affects dopamine
o Citalopram & escitalopram- true SSRIs
Orally, highly protein-bound and variable biodistribution, peak levels range from 1 to 8 hours
Significant first pass, metabolized by the CYP450 system, excreted by the kidneys
Contraindications- Hypersensitivity, MAOI, severe hepatic or renal impairment, avoided in the first and last
trimester of pregnancy
Adverse- Taper over the first week nausea/vomiting, headache, light-headedness, dizziness, dry mouth,
increased sweating, weight gain or loss, exacerbation of anxiety, agitation, sexual side effect
o Serotonin syndrome- (St. John’s wort & S-adenosylmethionine) Nausea, diarrhea, shivering,
sweating, hyperthermia, vasoconstriction, tachycardia, hypertension, myoclonic jerking, tremor,
agitation, ataxia, disorientation, confusion, and delirium
o Withdrawal symptoms- (paroxetine, sertraline, citalopram, escitalopram)- nausea, dizziness,
and paresthesia
o CNS depression- Avoid alcohol, antihistamines, opioid analgesics
Use- Depression, anxiety, panic disorder, OCD, and Bulimia. Premenstrual dysphoric disorder,
posttraumatic stress disorder, generalized anxiety disorder, and social phobia.
o Off-label anorexia, depressive phase of bipolar, chronic headaches, pain
Monitor- mood/suicidal ideations
Can take 2-6 weeks, but usually 3 to 4 weeks for full effect. Start low dose reduce side effects
WEAN MEDICATION SLOWLY, DO NOT ABRUPTLY STOP
, Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
Block the serotonin and norepinephrine transporters by inhibiting the reuptake of norepinephrine
and increasing the availability to bind with the postsynaptic receptors (Venlafaxine, duloxetine,
desvenlafaxine)
Metabolized by the liver, excreted by the urine
Contraindications- monitor for mood stability, Pregnancy category C, avoid pregnancy
Use- Major depression and bipolar mood disorders
o Venlafaxine- anxiety disorder, generalized anxiety disorder, social phobia, PTSD
o Duloxetine- neuropathic pain & overactive bladder
Adverse side effects- Headache, somnolence, dizziness, insomnia, nervousness, dry mouth,
constipation, abnormal ejaculation, anorexia/weight loss, elevated BP
Monitor- Liver function, suicidal risk, tapered off medication if pregnant, especially in the third
trimester, do not stop abruptly (withdrawal syndrome)
Atypical Antidepressants
Weak inhibits of presynaptic uptake of dopamine and norepinephrine. Does not inhibit the reuptake of
serotonin
Rapidly absorbed and bound to protein
Metabolized via CYP2D6,1A2, and 3A, 75% through urine and 15% in feces
Contraindicated in patients with seizures (severe head injury, severe stroke, CNS tumor, CNS
infection), anorexia nervosa or bulimia, withdrawal from alcohol, benzodiazepines, and
barbiturates, hypersensitivity
Adverse- Insomnia, headache, agitation, dizziness, diaphoresis, nausea/vomiting, xerostomia,
constipation
Off-label- Depression, Not indicated for depression and anxiety alone
Use- patients who do not respond well to SSRIs or have weight fain/sexual dysfunction
o Mirtazapine- drowsiness is helpful in patients who have insomnia as a symptom of
depression
o Combined with SSRI can help anxiety and depression, augment SSRIs
