ANTIDEPRESSANTS









Citalopram (Celexa®)

Dosage forms

Tablet
  • 10 mg
  • 20 mg
  • 40 mg

Dosing

Depression
  • Starting: 20 mg a day
  • Maintenance: 20 - 40 mg a day
  • Max: 40 mg a day
  • May take without regard to food
  • Max dose of 20 mg a day recommended for patients > 60 years old, and patients with liver disease
  • For patients who are poor CYP2C19 metabolizers, and patients taking CYP2C19 inhibitors, the maximum daily dose is 20 mg. See CYP2C19 for more.

Generic / Price

- YES/$

Mechanism of action

  • SSRI
  • Inhibits serotonin reuptake by neurons

FDA-approved indications

- Depression

Side effects



Side effect Citalopram Placebo
Nausea 21% 14%
Dry mouth 20% 14%
Somnolence 18% 10%
Insomnia 15% 14%
Increased sweating 11% 9%
Ejaculation disorder 6% 1%


Drug interactions


Contraindications / Precautions

  • Prolonged QT syndrome - citalopram should be stopped in patients with persistent QTc longer than 500 ms
  • Serotonin syndrome - may cause serotonin syndrome
  • Abnormal bleeding - through platelet inhibition
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Seizure - possible increase risk
  • Low sodium (hyponatremia) - may cause SIADH
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Poor CYP2C19 metabolizers - max dose 20 mg a day
  • Liver disease - maximum dose is 20 mg a day
  • Kidney disease
    • CrCl ≥ 30 ml/min: no dose adjustment necessary
    • CrCl < 30 ml/min: use caution

Escitalopram (Lexapro®)

Dosage forms

Tablet
  • 5 mg
  • 10 mg
  • 20 mg

Dosing - Depression

Adults
  • Starting: 10 mg once daily
  • Maintenance: 10 - 20 mg once daily
  • Max: 20 mg once daily
  • Liver disease: 10 mg once daily
  • Elderly: 10 mg once daily
  • May take without regard to food
  • Increase dose after a minimum of one week
Adolescents (12 - 17 years)
  • Starting: 10 mg once daily
  • Maintenance: 10 - 20 mg once daily
  • Max: 20 mg once daily
  • May take without regard to food
  • Increase dose after a minimum of three weeks

Dosing - GAD

Adults
  • Starting: 10 mg once daily
  • Maintenance: 10 - 20 mg once daily
  • Max: 20 mg once daily
  • Liver disease: 10 mg once daily
  • Elderly: 10 mg once daily
  • May take without regard to food
  • Increase dose after a minimum of one week

Efficacy


Generic / Price

- YES/$

Mechanism of action

  • SSRI
  • Inhibits serotonin reuptake by neurons

FDA-approved indications

  • Depression
  • Generalized anxiety disorder

Side effects



Side effect Escitalopram Placebo
Nausea 15% 7%
Insomnia 9% 4%
Ejaculation disorder (delay) 9% <1%
Diarrhea 8% 5%
Somnolence 6% 2%


Drug interactions


Contraindications / Precautions

  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Seizure - possible increase risk
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abnormal bleeding - through platelet inhibition
  • Low sodium (hyponatremia) - may cause SIADH
  • Prolonged QT syndrome - may worsen QT prolongation
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease - recommended dose is 10 mg a day
  • Kidney disease
    • CrCl ≥ 30 ml/min: no dose adjustment necessary
    • CrCl < 30 ml/min: use caution

Fluoxetine | Prozac® | Prozac weekly™ | Sarafem® | Symbyax® (fluoxetine + olanzapine)

Dosage forms

Fluoxetine capsule
  • 10 mg
  • 20 mg
  • 40 mg
Fluoxetine tablet
  • 10 mg
  • 20 mg
  • 60 mg
Fluoxetine solution
  • 20 mg/5 ml
  • Comes in bottle of 120 ml
Prozac Weekly®
  • 90 mg capsule
Sarafem® tablet
  • 10 mg
  • 15 mg
  • 20 mg
Symbyax® capsule
  • Olanzapine - Fluoxetine
    • 3 mg - 25 mg
    • 6 mg - 25 mg
    • 6 mg - 50 mg
    • 12 mg - 25 mg
    • 12 mg - 50 mg

Dosing - Prozac®

Depression (Adults)
  • Starting: 20 mg once daily
  • Maintenance: 20 - 40 mg once daily
  • Max: 80 mg once daily
  • May take without regard to food
Depression (Children and adolescents)
  • Starting: 10 - 20 mg once daily
  • Maintenance: 10 - 20 mg once daily
  • Max: 20 mg once daily
  • Lower weight children may only require 10 mg/day
  • In trials, children as young as 8 years old were included
  • May take without regard to food
OCD (Adults)
  • Starting: 20 mg once daily
  • Maintenance: 20 - 60 mg once daily
  • Max: 80 mg once daily
  • May take without regard to food
OCD (Adolescents and higher weight children)
  • Starting: 10 mg once daily for 2 weeks, then 20 mg once daily
  • Maintenance: 20 - 60 mg once daily
  • Max: 60 mg once daily
  • In trials, children as young as 7 years old were included
  • May take without regard to food
OCD (Lower weight children)
  • Starting: 10 mg once daily
  • Maintenance: 20 - 30 mg once daily
  • Max: 30 mg once daily
  • In trials, children as young as 7 years old were included
  • May take without regard to food
Bulimia nervosa (Adults)
  • Target dose: 60 mg once daily
  • Max: 60 mg once daily
  • In trials, only the 60 mg dose was superior to placebo
  • May take without regard to food
Panic disorder (Adults)
  • Starting: 10 mg once daily
  • Maintenance: 10 - 60 mg once daily
  • Max: 60 mg once daily
  • May take without regard to food

Dosing - Prozac weekly®

Depression (Adults)
  • 90 mg once a week
  • May take without regard to food

Dosing - Sarafem®

Premenstrual dysphoric disorder (Adults)
  • Continuous dosing: 20 mg once daily
  • Intermittent dosing: 20 mg once daily starting 14 days before menstruation through first full day of menses
  • May take without regard to food

Dosing - Symbyax®

Depression with Bipolar I and treatment-resistant depression (Adults)
  • Starting: 6/25 mg once daily in the evening
  • Maintenance: 6/25 mg - 12/50 mg once daily
  • Max: 18/75 mg once daily
  • May take without regard to food
  • See olanzapine for more
Depression with Bipolar I (10 - 17 years)
  • Starting: 3/25 mg once daily in the evening
  • Maintenance: 6/25 mg - 12/50 mg once daily
  • Max: 12/50 mg once daily
  • May take without regard to food
  • See olanzapine for more

Efficacy


Generic / Price

  • Prozac® (tablet and solution) - YES/$
  • Prozac weekly™ - YES/$$-$$$
  • Sarafem­ - NO/$$$$
  • Symbyax™ - YES/$$-$$$$

Other

  • Switching from daily Prozac to Prozac weekly - start Prozac weekly 7 days after last daily dose
  • Full effect of medication may not be seen for 4 weeks

Mechanism of action

  • SSRI
  • Inhibits serotonin reuptake by neurons

FDA-approved indications

Prozac®
  • Depression
  • Obsessive-Compulsive Disorder (OCD)
  • Bulimia Nervosa
  • Panic disorder
  • Premenstrual dysphoric disorder
Sarafem®
  • Premenstrual dysphoric disorder
Symbyax®
  • Depression associated with Bipolar 1
  • Treatment resistant depression

Side effects



Side effect Placebo
Nausea 22% 9%
Headache 21% 19%
Insomnia 19% 10%
Nervousness 13% 8%
Fatigue 11% 6%
Diarrhea 11% 7%
Decreased appetite 10% 3%
Abnormal ejaculation 7% 1%


Drug interactions

  • Thioridazine - DO NOT COMBINE
  • Pimozide (Orap®) - DO NOT COMBINE
  • MAO inhibitors - DO NOT COMBINE
  • Serotonergic drugs - may increase risk of serotonin syndrome
  • Drugs that prolong the QT interval - fluoxetine may prolong the QT interval. Use caution with other drugs that prolong the QT interval.
  • Anticoagulant/Antiplatelet meds - may increase bleeding risk
  • CYP2D6 substrates - fluoxetine is a strong CYP2D6 inhibitor
  • Tamoxifen - tamoxifen is metabolized by CYP2D6 to its active form. Some studies have found that tamoxifen is not as effective when taken with CYP2D6 strong inhibitors. Other studies have found no effect. See tamoxifen studies for more.

Precautions / Contraindications
  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Seizure - possible increase risk
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abnormal bleeding - through platelet inhibition
  • Low sodium (hyponatremia) - may cause SIADH
  • Prolonged QT syndrome - may worsen QT prolongation
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease - use lower or less frequent dose. Manufacturer makes no specific dosage recommendations.
  • Kidney disease - no dose adjustment necessary

Fluvoxamine | Luvox® | Luvox® CR

Dosage forms

Luvox® tablet
  • 25 mg
  • 50 mg
  • 100 mg
Luvox CR® capsule
  • 100 mg
  • 150 mg

Dosing - Luvox®

OCD (Adults)
  • Starting: 50 mg once daily at bedtime
  • Maintenance: 100 - 300 mg/day
  • Max: 300 mg/day
  • Doses > 100 mg should be given in 2 divided doses
  • Increase in increments of 50 mg/day every 4 - 7 days
OCD (Children 8 - 17 years)
  • Starting: 25 mg once daily at bedtime
  • Maintenance: 50 - 200 mg/day
  • Max: 300 mg/day
  • Doses > 50 mg should be given in 2 divided doses
  • Increase dose in increments of 25 mg/day every 4 - 7 days

Dosing - Luvox® CR

OCD (Adults)
  • Starting: 100 mg once daily at bedtime
  • Maintenance: 100 - 300 mg once daily
  • Max: 300 mg once daily
  • Increase in increments of 50 mg/day every 7 days

Generic / Price

  • Luvox® - YES/$
  • Luvox® CR - YES/$$-$$$

Other

  • May take without regard to food
  • Because of the potential for drug interactions, fluvoxamine is not widely used

Mechanism of action

  • SSRI
  • Inhibits serotonin reuptake by neurons

FDA-approved indications

- Obsessive-Compulsive Disorder (OCD)

Side effects



Side effect Fluvoxamine Placebo
Nausea 40% 14%
Somnolence 22% 8%
Headache 22% 20%
Insomnia 21% 10%
Fatigue 14% 6%
Dry mouth 14% 10%
Nervousness 12% 5%
Dizziness 11% 6%
Diarrhea 11% 7%
Delayed ejaculation 8% 1%


Drug interactions


Contraindications / Precautions

  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Seizure - possible increase risk
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abnormal bleeding - through platelet inhibition
  • Low sodium (hyponatremia) - may cause SIADH
  • Prolonged QT syndrome - may worsen QT prolongation
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease - clearance is decreased. Dose may need to be decreased. Manufacturer makes no specific dosage recommendations.
  • Kidney disease - kidney disease does not appear to affect clearance

Paroxetine | Paxil® | Paxil CR® | Brisdelle™ | Pexeva®

Dosage forms

Paxil® tablet
  • 10 mg
  • 20 mg
  • 30 mg
  • 40 mg
  • Paxil® is paroxetine HCL
Paxil CR® tablet
  • 12.5 mg
  • 25 mg
  • 37.5 mg
  • Paxil CR® is paroxetine HCL
Pexeva® tablet
  • 10 mg
  • 20 mg
  • 30 mg
  • 40 mg
  • Pexeva® is paroxetine mesylate
Brisdelle™ capsule
  • 7.5 mg
  • Brisdelle® is paroxetine mesylate

Dosing - Paxil®

Depression
  • Starting: 20 mg once daily
  • Maintenance: 20 - 50 mg once daily
  • Max: 50 mg once daily
  • Increase in increments of 10 mg/day every 7 days
  • Liver and kidney disease - initial dose 10 mg a day. Do not exceed 40 mg a day.
OCD
  • Starting: 20 mg once daily
  • Target: 40 mg once daily
  • Max: 60 mg once daily
  • Increase in increments of 10 mg/day every 7 days
Panic disorder
  • Starting: 10 mg once daily
  • Target: 40 mg once daily
  • Max: 60 mg once daily
  • Increase in increments of 10 mg/day every 7 days
Social anxiety disorder
  • Starting: 20 mg once daily
  • Maintenance: 20 - 60 mg once daily
  • Max: 60 mg once daily
  • Increase in increments of 10 mg/day every 7 days
Generalized anxiety disorder
  • Starting: 20 mg once daily
  • Target: 20 once daily
  • Max: 50 mg once daily
  • Increase in increments of 10 mg/day every 7 days
Posttraumatic stress disorder
  • Starting: 20 mg once daily
  • Target: 20 mg once daily
  • Max: 50 mg once daily
  • Increase in increments of 10 mg/day every 7 days

Dosing - Pexeva®

Depression
  • Starting: 20 mg once daily
  • Maintenance: 20 - 50 mg once daily
  • Max: 50 mg once daily
  • Increase in increments of 10 mg/day every 7 days
  • Liver and kidney disease - initial dose 10 mg a day. Do not exceed 40 mg a day.
OCD
  • Starting: 20 mg once daily
  • Target: 40 mg once daily
  • Max: 60 mg once daily
  • Increase in increments of 10 mg/day every 7 days
Panic disorder
  • Starting: 10 mg once daily
  • Target: 40 mg once daily
  • Max: 60 mg once daily
  • Increase in increments of 10 mg/day every 7 days
Generalized anxiety disorder
  • Starting: 20 mg once daily
  • Target: 20 once daily
  • Max: 50 mg once daily
  • Increase in increments of 10 mg/day every 7 days

Dosing - Paxil CR®

Depression
  • Starting: 25 mg once daily
  • Maintenance: 25 - 62.5 mg once daily
  • Max: 62.5 mg once daily
  • Increase in increments of 12.5 mg/day every 7 days
  • Liver and kidney disease - initial dose 12.5 mg a day. Do not exceed 50 mg a day.
Panic disorder
  • Starting: 12.5 mg once daily
  • Maintenance: 12.5 - 75 mg once daily
  • Max: 75 mg once daily
  • Increase in increments of 12.5 mg/day every 7 days
Social anxiety disorder
  • Starting: 12.5 mg once daily
  • Maintenance: 12.5 - 37.5 mg once daily
  • Max: 37.5 mg once daily
  • Increase in increments of 12.5 mg/day every 7 days
Premenstrual dysphoric disorder
  • Continuous: 12.5 - 25 mg once daily
  • Intermittent: 12.5 - 25 mg once daily during the luteal phase (days 14 - 28 of the menstrual cycle with day 1 being the first day of menses)

Dosing - Brisdelle™

Vasomotor symptoms associated with menopause
  • 7.5 mg once daily at bedtime

Generic / Price

  • Paxil® - YES/$
  • Paxil® CR - YES/$$
  • Pexeva® - NO/$$$$
  • Brisdelle™ - YES/$$-$$$

Other

All
  • May take without regard to food
Paxil® CR
  • Do not crush or chew tablet

Mechanism of action

  • SSRI
  • Inhibits serotonin reuptake by neurons

FDA-approved indications

Paxil®
  • Depression
  • Panic disorder
  • Social anxiety disorder
  • Generalized anxiety disorder
  • Posttraumatic stress disorder (PTSD)
Paxil® CR
  • Depression
  • Panic disorder
  • Social anxiety disorder
  • Premenstrual dysphoric disorder
Pexeva®
  • Depression
  • Obsessive-Compulsive Disorder (OCD)
  • Panic disorder
  • Generalized anxiety disorder
Brisdelle™
  • Vasomotor symptoms in menopause

Side effects



Side effect Paroxetine Placebo
Nausea 26% 9%
Somnolence 23% 9%
Headache 18% 17%
Dry Mouth 18% 12%
Fatigue 15% 6%
Constipation 14% 9%
Dizziness 13% 6%
Insomnia 13% 6%
Ejaculatory delay 13% 0%
Diarrhea 12% 8%
Sweating 11% 2%
Other male sexual dysfunction 10% 0%


Drug interactions

  • MAO inhibitors - DO NOT COMBINE
  • Pimozide (Orap®) - DO NOT COMBINE
  • Thioridazine - DO NOT COMBINE
  • Cimetidine (Tagamet®) - may increase paroxetine levels
  • Risperidone (Risperdal®) - may increase risperidone levels
  • Tricyclic antidepressants (TCA) - may increase TCA levels
  • Fosamprenavir/Ritonavir - may decrease paroxetine levels
  • Drugs that prolong the QT interval - may potentiate QT prolongation
  • Serotonergic drugs - may increase risk of serotonin syndrome
  • Anticoagulant/Antiplatelet meds - may increase bleeding risk
  • CYP2D6 substrates - paroxetine is a strong CYP2D6 inhibitor
  • Tamoxifen - tamoxifen is metabolized by CYP2D6 to its active form. Some studies have found that tamoxifen is not as effective when taken with CYP2D6 strong inhibitors. Other studies have found no effect. See tamoxifen studies for more.

Contraindications / Precautions

  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Seizure - possible increase risk
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abnormal bleeding - through platelet inhibition
  • Low sodium (hyponatremia) - may cause SIADH
  • Prolonged QT syndrome - may worsen QT prolongation
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease
    • Paxil, Pexeva
      • Severe (Child-Pugh C): starting - 10 mg/day; do not exceed 40 mg/day
    • Paxil CR
      • Severe (Child-Pugh C): starting - 12.5 mg/day; do not exceed 50 mg/day
    • Brisdelle
      • No dose adjustment necessary
  • Kidney disease
    • Paxil, Pexeva
      • CrCl 30 - 60 ml/min: paroxetine levels increase 2-fold; use caution
      • CrCl < 30 ml/min: starting - 10 mg/day; do not exceed 40 mg/day
    • Paxil CR
      • CrCl 30 - 60 ml/min: paroxetine levels increase 2-fold; use caution
      • CrCl < 30 ml/min: starting - 12.5 mg/day; do not exceed 50 mg/day
    • Brisdelle
      • No dose adjustment necessary

Sertraline (Zoloft®)

Dosage forms

Tablet
  • 25 mg
  • 50 mg
  • 100 mg
Oral concentrate
  • 20 mg/ml
  • Comes in 60 ml bottle
  • Contains 12% alcohol

Dosing

Depression
  • Starting: 50 mg once daily
  • Maintenance: 50 - 200 mg once daily
  • Max: 200 mg once daily
  • May take without regard to food
  • Increase dose at intervals of ≥ 1 week
OCD (Adults)
  • Starting: 50 mg once daily
  • Maintenance: 50 - 200 mg once daily
  • Max: 200 mg once daily
  • May take without regard to food
  • Increase dose at intervals of ≥ 1 week
OCD (Children and adolescents)
  • Starting (6 - 12 years old): 25 mg once daily
  • Starting (13 - 17 years old): 50 mg once daily
  • Maintenance: 50 - 200 mg once daily
  • Max: 200 mg once daily
  • May take without regard to food
  • Increase dose at intervals of ≥ 1 week
Panic disorder, PTSD, Social anxiety disorder
  • Starting: 25 mg once daily
  • Maintenance: 50 - 200 mg once daily
  • Max: 200 mg a day
  • May take without regard to food
  • Increase dose at intervals of ≥ 1 week
Premenstrual dysphoric disorder
  • Continuous: 50 - 150 mg once daily
  • Intermittent: 50 - 100 mg once daily during the luteal phase (days 14 - 28 of the menstrual cycle with day 1 being the first day of menses)
  • May take without regard to food
  • Increase dose at the onset of each new cycle
  • For 100 mg/day intermittent dosing, use 50 mg/day for first 3 days of each new cycle

Efficacy


Generic / Price

  • Tablet - YES/$
  • Concentrate (60 ml) - YES/$

Other

Oral concentrate
  • Must be diluted before use. Just before taking, use the dropper provided to remove the required amount and mix with 4 oz (1/2 cup) of water, ginger ale, lemon/lime soda, lemonade or orange juice ONLY. Do not mix with anything other than the liquids listed. The dose should be taken immediately after mixing. Do not mix in advance.
  • At times, a slight haze may appear after mixing; this is normal
  • The dropper contains dry natural rubber. Use caution in patients with latex allergy.

Mechanism of action

  • Selective Serotonin Reuptake Inhibitor (SSRI)
  • Inhibits serotonin reuptake by neurons

FDA-approved indications

  • Depression
  • Obsessive-Compulsive Disorder (OCD)
  • Panic disorder
  • Posttraumatic Stress Disorder (PTSD)
  • Premenstrual Dysphoric Disorder
  • Social Anxiety Disorder

Side effects



Side effect Sertraline Placebo
Nausea 25% 11%
Headache 25% 23%
Insomnia 21% 11%
Diarrhea 20% 10%
Ejaculation failure 14% 1%
Dry Mouth 14% 8%
Somnolence 13% 7%
Dizziness 12% 7%
Fatigue 12% 7%


Drug interactions


Contraindications / Precautions

  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Seizure - possible increase risk
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abnormal bleeding - through platelet inhibition
  • Low sodium (hyponatremia) - may cause SIADH
  • Prolonged QT syndrome - may worsen QT prolongation
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease - clearance is decreased. Use caution. Decrease dose or frequency.
  • Kidney disease - no dose adjustment necessary



Desvenlafaxine Succinate | Pristiq® | Khedezla™

Dosage forms

Pristiq® extended-release tablet
  • 25 mg
  • 50 mg
  • 100 mg
Khedezla™ extended-release tablet
  • 50 mg
  • 100 mg

Dosing

Depression (Pristiq® and Khedezla™)
  • Starting: 50 mg once daily
  • Maintenance: 50 - 400 mg once daily
  • Max: 400 mg once daily
  • Pristiq and Khedezla are not considered therapeutically equivalent and cannot be substituted for each other

Generic / Price

  • Pristiq® - YES/$
  • Khedezla™ - YES/$$$$

Other

Pristiq®, Khedezla™
  • May take without regard to food
  • Take at approximately the same time every day
  • Do not cut, crush, or chew tablet
  • In trials, no additional benefit was seen at doses greater than 50 mg a day

Mechanism of action

  • Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)
  • Inhibits serotonin and norepinephrine reuptake by neurons

FDA-approved indications

- Depression

Side effects



Side effect Desvenlafaxine 100 mg/day Placebo
Nausea 26% 10%
Dry Mouth 17% 9%
Insomnia 12% 6%
Sweating 11% 4%
Dizziness 10% 5%
Constipation 9% 4%
Ejaculation delay 5% < 1%
Erectile dysfunction 6% 1%
  • Orthostatic hypotension - 8% of patients ≥ 65 years
  • Elevated blood pressure - desvenlafaxine may cause an increase in blood pressure. Effect is typically small. Average SBP increase 2 - 4 mmHg.
  • Elevated cholesterol - desvenlafaxine may raise cholesterol levels (4 - 10% of patients)


Drug interactions

  • MAO inhibitors - DO NOT COMBINE. Do not start an MAO inhibitor within 7 days of stopping desvenlafaxine . Do not start desvenlafaxine within 14 days of stopping an MAO inhibitor.
  • Serotonergic drugs - may increase risk of serotonin syndrome
  • Anticoagulant/Antiplatelet meds - desvenlafaxine may increase bleeding risk when taken with drugs that affect hemostasis
  • CYP2D6 substrates - desvenlafaxine is a weak CYP2D6 inhibitor. When taking desvenlafaxine 400 mg a day, may need to half dose of sensitive CYP2D6 substrates.
  • CYP3A4 strong inhibitors - desvenlafaxine is a minor substrate of CYP3A4. Strong CYP3A4 inhibitors may increase desvenlafaxine levels.

Contraindications / Precautions

  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Seizure - possible increase risk
  • Hypertension - may raise blood pressure
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abnormal bleeding - serotonin is involved in platelet activation. Desvenlafaxine may inhibit serotonin uptake by platelets and increase the risk of bleeding.
  • Low sodium (hyponatremia) - may cause SIADH
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease
    • Moderate-severe disease (Child-Pugh B and C): recommended dose is 50 mg/day; do not exceed 100 mg/day
  • Kidney disease
    • CrCl 30 - 50 ml/min: max dose is 50 mg a day
    • CrCl < 30 ml/min: max dose is 25 mg every day or 50 mg every other day

Duloxetine (Cymbalta®)

Dosage forms

Cymbalta® capsule
  • 20 mg
  • 30 mg
  • 60 mg

Dosing

Depression
  • Starting: 30 - 60 mg/day
  • Maintenance: 40 - 60 mg/day
  • Max: 120 mg/day
  • May be given once daily or in two divided doses
  • May take without regard to food
Generalized anxiety disorder
  • Adults
  • Starting: 30 - 60 mg once daily
  • Maintenance: 60 - 120 mg once daily
  • Max: 120 mg once daily
  • For elderly patients, starting dose should be 30 mg once daily. Increase to 60 mg once daily after 2 weeks.
  • May take without regard to food
  • Children 7 - 17 years
  • Starting: 30 mg once daily
  • Maintenance: 30 - 60 mg once daily
  • Max: 120 mg/day
  • Increase dose in increments of 30 mg/day at intervals of ≥ 2 weeks
  • May take without regard to food
Diabetic peripheral neuropathy
  • Starting: 30 - 60 mg once daily
  • Target: 60 mg once daily
  • Max: 60 mg once daily
  • May take without regard to food
Fibromyalgia
  • Starting: 30 - 60 mg once daily
  • Target: 60 mg once daily
  • Max: 60 mg once daily
  • May take without regard to food
Chronic musculoskeletal pain
  • Starting: 30 - 60 mg once daily
  • Target: 60 mg once daily
  • Max: 60 mg once daily
  • May take without regard to food

Generic / Price

- YES/$

Other

  • Do not open, crush, or chew capsule
  • In most studies, doses > 60 mg a day have not shown additional benefit

Mechanism of action

  • Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)
  • Inhibits serotonin and norepinephrine reuptake by neurons

FDA-approved indications

  • Depression
  • Generalized anxiety disorder
  • Diabetic peripheral neuropathy
  • Fibromyalgia
  • Chronic musculoskeletal pain

Side effects



Side effect Duloxetine Placebo
Nausea 23% 8%
Dry Mouth 14% 6%
Headache 14% 14%
Constipation 9% 4%
Diarrhea 9% 6%
Fatigue 9% 5%
Somnolence 9% 3%
Insomnia 9% 5%
Erectile dysfunction 4% 1%
Ejaculation delay 2% 1%
Elevated liver enzymes (> 3X upper limit of normal) 1.25% 0.45%
  • Elevated blood pressure - duloxetine may cause an increase in blood pressure. Effect is typically small. Average SBP increase 1 - 2 mmHg at typical dosing.
  • Orthostatic hypotension - may occur in some patients


Drug interactions


Contraindications / Precautions

  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Seizure - possible increase risk
  • Hypertension - may raise blood pressure
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abnormal bleeding - through platelet inhibition
  • Decreased gastric motility - may affect absorption
  • Low sodium (hyponatremia) - may cause SIADH
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease - do not use in patients with significant liver disease
  • Kidney disease
    • CrCl ≥ 30 ml/min: no dose adjustment necessary
    • CrCl < 30 ml/min: DO NOT USE

Levomilnacipran (Fetzima™)

Dosage forms

Extended-release capsule
  • 20 mg
  • 40 mg
  • 80 mg
  • 120 mg
Titration pack:
  • 20 mg capsule X 2
  • 40 mg capsule X 26

Dosing

Depression
  • Starting: 20 mg once daily for 2 days, then 40 mg once daily
  • Maintenance: 40 - 120 mg once daily
  • Max: 120 mg once daily
  • Increase in increments of 40 mg/day at intervals of ≥ 2 days
  • May take without regard to food
Dosing in kidney disease
  • CrCl ≥ 60 ml/min: no dose adjustment necessary
  • CrCl 30 - 59 ml/min: do not exceed 80 mg a day
  • CrCl 15 - 29 ml/min: do not exceed 40 mg/day
  • CrCl < 15 ml/min: not recommended
Dosing with strong CYP3A4 inhibitors
  • Do not exceed 80 mg a day
  • See CYP3A4 for more

Generic / Price

- NO/$$$$

Other

  • Do not open, chew, or crush capsule

Mechanism of action

  • Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)
  • Inhibits serotonin and norepinephrine reuptake by neurons

FDA-approved indications

- Depression

Side effects



Side effect Fetzima Placebo
Nausea 17% 6%
Constipation 9% 3%
Excessive sweating 9% 2%
Erectile dysfunction 6% 1%
Rapid heart beat 6% 2%
Urinary hesitancy / retention 5% 0%
Ejaculation disorder 5% <1%
Vomiting 5% 1%
Palpitations 5% 1%
Testicular pain 4% <1%
Hot flush 3% 1%
Orthostatic hypotension 3% 1%
Decreased appetite 3% 1%
  • Elevated blood pressure - levomilnacipran may cause an increase in blood pressure. Effect is typically small. Average SBP increase 3 - 4 mmHg, average DBP increase 3 mmHg.
  • Increase in heart rate - levomilnacipran may cause an increase in heart rate. Average increase of 7-9 bpm in studies



Drug interactions

  • MAO inhibitors - DO NOT COMBINE
  • Alcohol - alcohol may accelerate drug release from the levomilnacipran capsule. It is recommended that it not be taken with alcohol.
  • CYP3A4 strong inhibitors - levomilnacipran is a CYP3A4 sensitive substrate. The dose of levomilnacipran should not exceed 80 mg a day when taken with CYP3A4 strong inhibitors
  • Serotonergic drugs - may increase risk of serotonin syndrome
  • Anticoagulant/Antiplatelet meds - may increase bleeding risk

Contraindications / Precautions

  • Uncontrolled narrow-angle glaucoma - DO NOT USE
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Urinary retention (e.g. BPH) - levomilnacipran may worsen urinary retention in certain conditions
  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Seizure - possible increase risk
  • Hypertension - may raise blood pressure
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abnormal bleeding - through platelet inhibition
  • Low sodium (hyponatremia) - may cause SIADH
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease - no dose adjustment necessary
  • Kidney disease
    • CrCl ≥ 60 ml/min: no dose adjustment necessary
    • CrCl 30 - 59 ml/min: do not exceed 80 mg a day
    • CrCl 15 - 29 ml/min: do not exceed 40 mg/day
    • CrCl < 15 ml/min: not recommended

Venlafaxine |Effexor® | Effexor XR®

Dosage forms

Effexor® tablet
  • 25 mg
  • 37.5 mg
  • 50 mg
  • 75 mg
  • 100 mg
Effexor XR® extended-release capsule
  • 37.5 mg
  • 75 mg
  • 150 mg
Effexor XR® extended-release tablet
  • 37.5 mg
  • 75 mg
  • 150 mg
  • 225 mg

Dosing - Effexor®

Depression
  • Starting: 75 mg a day
  • Maintenance: 75 - 225 mg a day
  • Max: 375 mg a day
  • Give in 2 to 3 divided doses
  • Increase dose in increments of up to 75 mg/day at intervals of ≥ 4 days
  • Doses higher than 225 mg a day have not been extensively studied
  • Take with food to help reduce nausea

Dosing - Effexor XR®

Depression
  • Starting: 37.5 - 75 mg once daily
  • Maintenance: 75 - 225 mg once daily
  • Max: 225 mg once daily
  • Increase dose in increments of up to 75 mg/day at intervals of ≥ 4 days
  • Take with food to help reduce nausea
Generalized anxiety disorder
  • Starting: 37.5 - 75 mg once daily
  • Maintenance: 75 - 225 mg once daily
  • Max: 225 mg once daily
  • Increase dose in increments of up to 75 mg/day at intervals of ≥ 4 days
  • Take with food to help reduce nausea
Social anxiety disorder
  • Target: 75 mg once daily
  • There is no evidence that higher doses are beneficial
  • Take with food to help reduce nausea
Panic disorder
  • Starting: 37.5 once daily
  • Maintenance: 75 - 225 mg once daily
  • Max: 225 mg once daily
  • Increase dose in increments of up to 75 mg/day at intervals of ≥ 7 days
  • Take with food to help reduce nausea
Migraine prevention (off-label)
  • 75 - 150 mg/day
Diabetic neuropathy (off-label)

Generic / Price

  • Effexor® - YES/$
  • Effexor XR® capsule - YES/$
  • Effexor XR® tablet - YES/$$

Other

Effexor®
  • May cause false-positive urine drug tests for phencyclidine (PCP) and amphetamines
Effexor XR®
  • May cause false-positive urine drug tests for phencyclidine (PCP) and amphetamines
  • Capsules may be opened and sprinkled on applesauce. Do not chew contents.
  • Do not crush, cut, or chew tablet
Switching brands
  • When switching between Effexor® and Effexor XR®, keep total daily dose the same

Mechanism of action

  • Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)
  • Inhibits serotonin and norepinephrine reuptake by neurons
  • Weak dopamine reuptake inhibitor

FDA-approved indications

  • Depression
  • Generalized anxiety disorder
  • Social anxiety disorder
  • Panic disorder

Side effects



Side effect Venlafaxine Placebo
Nausea 35% 12%
Dizziness 16% 11%
Dry Mouth 16% 6%
Insomnia 15% 10%
Somnolence 14% 8%
Fatigue 12% 8%
Ejaculation delay/abnormal 11% < 1%
Constipation 10% 4%
Sweating 10% 3%
  • Elevated blood pressure - venlafaxine may cause an increase in blood pressure. The effect increases with higher doses.
  • Elevated cholesterol - venlafaxine may raise cholesterol levels (5.3% of patients)

Drug interactions

  • MAO inhibitors - DO NOT COMBINE
  • Cimetidine (Tagamet®) - may increase venlafaxine levels
  • Haloperidol (Haldol®) - may increase haloperidol levels
  • Desipramine - may increase desipramine levels
  • Metoprolol - may increase metoprolol levels
  • Risperidone (Risperdal®) - may increase risperidone levels
  • Indinavir (Crixivan®) - may decrease indinavir levels
  • Drugs that prolong the QT interval - may potentiate QT prolongation
  • Serotonergic drugs - may increase risk of serotonin syndrome
  • Anticoagulant/Antiplatelet meds - may increase bleeding risk
  • CYP2D6 inhibitors and substrates - venlafaxine is a CYP2D6 sensitive substrate and CYP2D6 weak inhibitor
  • CYP3A4 inhibitors - may increase venlafaxine levels

Contraindications / Precautions

  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Seizure - possible increase risk
  • Hypertension - may raise blood pressure
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abnormal bleeding - through platelet inhibition
  • Low sodium (hyponatremia) - may cause SIADH
  • Prolonged QT syndrome - may worsen QT prolongation
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease
    • Effexor, Effexor XR
      • Mild-moderate disease (Child-Pugh A/B): reduce dose by 50%
      • Severe (Child-Pugh C): reduce dose by 50% or more
  • Kidney disease
    • Effexor
      • CrCl 30 - 90 ml/min: reduce dose by 25%
      • CrCl < 30 ml/min: reduce dose by 50%
    • Effexor XR
      • CrCl 30 - 90 ml/min: reduce dose by 25% - 50%
      • CrCl < 30 ml/min: reduce dose by 50% or more



Bupropion | Wellbutrin® | Wellbutrin SR® | Wellbutrin XL® | Zyban® | Aplenzin® | Forfivo XL™ | Contrave®

Dosage forms

Wellbutrin® tablet
  • 75 mg
  • 100 mg
Wellbutrin SR® tablet
  • 100 mg
  • 150 mg
  • 200 mg
Wellbutrin XL® tablet
  • 150 mg
  • 300 mg
Forfivo XL™ tablet
  • 450 mg
Zyban® tablet
  • 150 mg
Aplenzin® tablet
  • 174 mg
  • 348 mg
  • 522 mg
  • Aplenzin® is bupropion hydrobromide
Contrave®

Dosing - Depression

Wellbutrin®
  • Starting: 100 mg twice a day for 3 days
  • Maintenance: 100 mg three times a day
  • Max: 450 mg a day
  • May take without regard to food
Wellbutrin SR®
  • Starting: 150 mg once a day for 3 days
  • Maintenance: 150 mg twice a day
  • Max: 200 mg twice a day
  • May take without regard to food
Wellbutrin XL®
  • Starting: 150 mg once daily
  • Maintenance: 300 mg once daily
  • Max: 450 mg once daily
  • Increase dose at intervals ≥ 4 days
  • May take without regard to food
Aplenzin®
  • Starting: 174 mg once daily for 4 days
  • Maintenance: 348 mg once daily
  • Max: 522 mg once daily
  • May take without regard to food
  • Aplenzin-Wellbutrin XL equivalence:174 mg = 150 mg, 348 mg = 300 mg, 522 = 450 mg
Forfivo XL™
  • Starting: use another form of bupropion to initiate therapy
  • Maintenance: 450 mg once daily
  • Max: 450 mg once daily
  • May take without regard to food

Dosing - SAD

Wellbutrin XL®
  • Starting: 150 mg once daily
  • Target: 300 mg once daily
  • Max: 300 mg once daily
  • Increase dose at intervals ≥ 7 days
  • May take without regard to food
Aplenzin®
  • Starting: 174 mg once daily
  • Target: 348 mg once daily
  • Max: 348 mg once daily
  • Increase dose at intervals ≥ 7 days
  • May take without regard to food
  • Aplenzin-Wellbutrin XL equivalence:174 mg = 150 mg, 348 mg = 300 mg, 522 = 450 mg

Dosing - Smoking cessation

Zyban®
  • Starting: 150 mg once daily for 3 days
  • Maintenance: 150 mg twice a day
  • Max: 150 mg twice a day
  • May take without regard to food

Dosing - Weight loss

Contrave® (naltrexone + bupropion)

Efficacy


Generic / Price

  • Wellbutrin® - YES/$
  • Wellbutrin SR® - YES/$
  • Wellbutrin XL® - YES/$
  • Forfivo XL™ - NO/$$$$
  • Aplenzin® - NO/$$$$
  • Zyban® - YES/$-$$

Other

All
  • May take without regard to food
  • Do not crush, cut, or chew tablets
  • May cause false-positive urine drug tests for amphetamines
Switching brands
  • When switching between Wellbutrin®, Wellbutrin SR®, and Wellbutrin XL®, keep total daily dose the same

Mechanism of action

  • Norepinephrine-Dopamine Reuptake Inhibitor
  • Inhibits norepinephrine and dopamine reuptake by neurons

FDA-approved indications

  • Depression
  • Seasonal affective disorder
  • Smoking cessation

Side effects



Side effect Bupropion Placebo
Agitation 32% 22%
Dry mouth 28% 18%
Constipation 26% 17%
Headache 26% 22%
Nausea 23% 19%
Excessive sweating 22% 15%
Dizziness 22% 16%
Tremor 21% 8%
Insomnia 19% 16%
Blurred vision 15% 10%
Rapid heart beat 11% 9%
  • Increased blood pressure - may increase blood pressure. Incidence is unknown.


Drug interactions

  • MAO inhibitors - DO NOT COMBINE
  • CYP2B6 inhibitors and inducers - bupropion is a CYP2B6 sensitive substrate
  • CYP2D6 substrates - bupropion is a CYP2D6 strong inhibitor
  • OCT2 substrates - bupropion is an OCT2 inhibitor
  • Amantadine - may increase side effects
  • Clopidogrel (Plavix®) - clopidogrel is a CYP2B6 inhibitor and may raise bupropion levels. Bupropion doses may need to be decreased when taken with clopidogrel.
  • Digoxin - bupropion may decrease digoxin levels. Monitor digoxin levels when taking together.
  • Levodopa (Sinemet®) - may increase side effects
  • Drugs that increase dopaminergic or noradrenergic activity - may increase risk of hypertension
  • Ritonavir, Lopinavir, and Efavirenz - ritonavir, lopinavir, and efavirenz are CYP2B6 inducers and may lower bupropion levels to subtherapeutic levels
  • Tamoxifen - tamoxifen is metabolized by CYP2D6 to its active form. Some studies have found that tamoxifen is not as effective when taken with CYP2D6 strong inhibitors. Other studies have found no effect. See tamoxifen studies for more.

Contraindications / Precautions

  • Seizure disorder - DO NOT USE. Bupropion carries the highest seizure risk of all the antidepressants.
  • Bulimia or anorexia nervosa - DO NOT USE. These patients have a higher risk of seizure.
  • Alcohol/benzodiazepine/barbiturate withdrawal - DO NOT USE. These patients have a higher risk of seizure.
  • Antiepileptic drug withdrawal - DO NOT USE. These patients have a higher risk of seizure.
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease
    • Wellbutrin
      • Mild (Child-Pugh A): consider dose/frequency reduction
      • Moderate-severe (Child-Pugh B/C): do not exceed 75 mg a day
    • Wellbutrin SR
      • Mild (Child-Pugh A): consider dose/frequency reduction
      • Moderate-severe (Child-Pugh B/C): max dose is 100 mg a day or 150 mg every other day
    • Wellbutrin XL, Zyban
      • Mild (Child-Pugh A): consider dose/frequency reduction
      • Moderate-severe (Child-Pugh B/C): max dose is 150 mg every other day
    • Aplenzin
      • Severe (Child-Pugh C): max dose is 174 mg every other day
    • Forfivo XL
      • Liver disease not recommended since only one dose
  • Kidney disease
    • CrCl < 90 ml/min: consider dose/frequency reduction
    • Forfivo XL is not recommended since only one dose



Amitriptyline (Elavil®)

Dosage forms

Tablet
  • 10 mg
  • 25 mg
  • 50 mg
  • 75 mg
  • 100 mg
  • 150 mg

Dosing

Depression
  • Starting: 25- 50 mg once daily
  • Maintenance: 50 - 100 mg once daily
  • Max: 150 mg once daily
  • May take without regard to food
Migraine prevention (off-label)
  • 25 - 150 mg/day
  • May take without regard to food
Diabetic neuropathy (off-label)
  • Starting: 10 - 25 mg once daily
  • Target: 25 - 100 mg/day
  • May take without regard to food
  • See diabetic neuropathy for more

Efficacy


Generic / Price

- YES/$

Mechanism of action

  • Tricyclic antidepressant
  • Inhibits norepinephrine and serotonin reuptake by neurons

FDA-approved indications

- Depression

Side effects

NOTE: Side effect profile not well-defined. Clomipramine is another TCA. It has the most extensive side effect information available. (see clomipramine for more)
  • Dry mouth - > 50% of patients in some trials
  • Drowsiness - common
  • Blurred vision
  • Constipation
  • Urinary retention
  • Postural hypotension

Drug interactions


Contraindications / Precautions

  • Seizure - may increase risk
  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Urinary retention - may worsen
  • Prolonged QT syndrome - may worsen QT prolongation
  • Abnormal bleeding - through platelet inhibition
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease - use caution
  • Kidney disease - use caution

Clomipramine (Anafranil™)

Dosage forms

Capsule
  • 25 mg
  • 50 mg
  • 75 mg

Dosing

Obsessive compulsive disorder
  • Starting: 25 mg a day
  • Maintenance: 100 mg a day
  • Max: 250 mg a day
  • When initiating, increase to 100 mg a day over the course of 2 weeks
  • May be given in divided doses to decrease gastrointestinal side effects
  • Take with food to limit GI side effects

Generic / Price

- YES/$$-$$$

Other

  • Gradually increase dose. May give twice a day when initiating to limit side effects.

Mechanism of action

  • Tricyclic antidepressant
  • Inhibits norepinephrine and serotonin reuptake by neurons

FDA-approved indications

- Obsessive-compulsive disorder (OCD)

Side effects



Side effect Clomipramine Placebo
Dry mouth 84% 17%
Somnolence 54% 16%
Tremor 54% 2%
Dizziness 54% 14%
Headache 52% 41%
Constipation 47% 11%
Ejaculation failure 42% 2%
Nausea 33% 14%
Increased sweating 29% 3%
Insomnia 25% 15%
Libido change 21% 3%
Impotence 20% 3%
Weight gain 18% 1%
Abnormal vision 18% 4%
Nervousness 18% 2%
Urinary retention 14% 2%
Diarrhea 13% 9%
Myalgia 13% 9%
Muscle twitching 13% 0%
Increased appetite 11% 2%
  • Orthostatic hypotension
  • Elevated liver enzymes - 1 - 3% of patients


Drug interactions


Contraindications / Precautions

  • Seizure - may increase risk
  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Urinary retention - may worsen
  • Prolonged QT syndrome - may worsen QT prolongation
  • Abnormal bleeding - through platelet inhibition
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease - use caution
  • Kidney disease - use caution

Desipramine (Norpramin®)

Dosage forms

Tablet
  • 10 mg
  • 25 mg
  • 50 mg
  • 75 mg
  • 100 mg
  • 150 mg

Dosing

Depression
  • Starting: 50 mg/day
  • Maintenance: 100 - 200 mg/day
  • Max: 300 mg/day
  • May be given once daily or in divided doses
  • May take without regard to food

Generic / Price

- YES/$

Mechanism of action

  • Tricyclic antidepressant
  • Inhibits norepinephrine and serotonin reuptake by neurons

FDA-approved indications

- Depression

Side effects

NOTE: Side effect profile not well-defined. Clomipramine is another TCA. It has the most extensive side effect information available. (see clomipramine for more)
  • Dry mouth - > 50% of patients in some trials
  • Drowsiness - common
  • Blurred vision
  • Constipation
  • Urinary retention
  • Postural hypotension

Drug interactions


Contraindications / Precautions

  • Seizure - may increase risk
  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Urinary retention - may worsen
  • Prolonged QT syndrome - may worsen QT prolongation
  • Abnormal bleeding - through platelet inhibition
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease - use caution
  • Kidney disease - use caution

Imipramine | Tofranil™ | Tofranil-PM™

Dosage forms

Tofranil™ tablet
  • 10 mg
  • 25 mg
  • 50 mg
Tofranil-PM™ capsule
  • 75 mg
  • 100 mg
  • 125 mg
  • 150 mg

Dosing - Depression

Tofranil™
  • Starting: 75 mg a day
  • Maintenance: 50 - 150 mg a day
  • Max: 200 mg a day
  • May be given once daily or in divided doses
  • May take without regard to food
Tofranil PM™
  • Starting: 75 mg a day
  • Maintenance: 75 - 150 mg a day
  • Max: 200 mg a day
  • May be given once daily or in divided doses
  • May take without regard to food

Dosing - Enuresis (≥ 6 years old)

Tofranil™
  • Starting: 25 mg one hour before bedtime
  • Maintenance:(6-11 years) 25 - 50 mg at night (≥ 12 years) 25 - 75 mg at night
  • Max: 2.5 mg/kg/day or 75 mg a day, whichever is less
  • For early bedwetters, a divided dose of 25 mg given midafternoon and repeated at bedtime may be more effective
  • May take without regard to food

Generic / Price

  • Tofranil™ - YES/$
  • Tofranil PM™ - YES/$$$$

Mechanism of action

  • Tricyclic antidepressant
  • Inhibits norepinephrine and serotonin reuptake by neurons

FDA-approved indications

Tofranil™
  • Depression
  • Childhood enuresis (bedwetting)
Tofranil PM™
  • Depression

Side effects

NOTE: Side effect profile not well-defined. Clomipramine is another TCA. It has the most extensive side effect information available. (see clomipramine for more)
  • Dry mouth - > 50% of patients in some trials
  • Drowsiness - common
  • Blurred vision
  • Constipation
  • Urinary retention
  • Postural hypotension

Drug interactions


Contraindications / Precautions

  • Seizure - may increase risk
  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Urinary retention - may worsen
  • Prolonged QT syndrome - may worsen QT prolongation
  • Abnormal bleeding - through platelet inhibition
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease - use caution
  • Kidney disease - use caution

Nortriptyline (Pamelor™)

Dosage forms

Capsule
  • 10 mg
  • 25 mg
  • 50 mg
  • 75 mg

Dosing

Depression
  • Starting: 25 mg a day
  • Maintenance: 25 - 100 mg a day given in 1 - 4 divided doses
  • Max: 150 mg a day
  • May take without regard to food
Herpes zoster neuralgia (off-label)
  • Starting: 25 mg at bedtime
  • Max: 150 mg a day
  • Increase by 25 mg daily every 2–3 days as tolerated
  • May take without regard to food
  • Dosing recommendation from the Infectious Disease Society of America

Generic / Price

- YES/$

Other

  • When taking doses > 100 mg a day, plasma levels of nortriptyline should be monitored. Ideal plasma level is 50 - 150 ng/ml.

Mechanism of action

  • Tricyclic antidepressant
  • Inhibits norepinephrine and serotonin reuptake by neurons

FDA-approved indications

- Depression

Side effects

NOTE: Side effect profile not well-defined. Clomipramine is another TCA. It has the most extensive side effect information available. (see clomipramine for more)
  • Dry mouth - > 50% of patients in some trials
  • Drowsiness - common
  • Blurred vision
  • Constipation
  • Urinary retention
  • Postural hypotension

Drug interactions


Contraindications / Precautions

  • Seizure - may increase risk
  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Urinary retention - may worsen
  • Prolonged QT syndrome - may worsen QT prolongation
  • Abnormal bleeding - through platelet inhibition
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease - use caution
  • Kidney disease - use caution



Trazodone | Desyrel® | Oleptro™

Dosage forms

Trazodone tablet
  • 50 mg
  • 100 mg
  • 150 mg
  • 300 mg
Oleptro® extended-release tablet
  • 150 mg
  • 300 mg

Dosing - Depression

Trazodone
  • Starting: 150 mg a day given in divided doses
  • Maintenance: 150 - 400 mg a day given in divided doses
  • Max: 400 mg a day
  • Increase dose by 50 mg/day every 3 - 4 days
  • When taken after a meal or light snack, absorption is increased
Oleptro™
  • Starting: 150 mg once daily
  • Maintenance: 150 - 300 mg once daily
  • Max: 375 mg once daily
  • Increase dose by 75 mg/day every 3 days
  • Oleptro™ should be taken on an empty stomach, preferably at bedtime

Dosing - Insomnia (off-label)

Trazodone
  • Starting: 50 mg at bedtime
  • Maintenance: 50 - 150 mg at bedtime
  • When taken after a meal or light snack, absorption is increased

Generic / Price

  • Trazodone - YES/$
  • Oleptro™ - NO/$$$

Other

Trazodone
  • Trazodone tablets are scored and can be broken in half
Oleptro™
  • Oleptro™ tablets are scored and can be broken in half. Tablets should not be crushed or chewed.

Mechanism of action

  • Serotonin modulator
  • Blocks postsynaptic serotonin receptors and inhibits postsynaptic serotonin reuptake

FDA-approved indications

- Depression

Side effects



Side effect Trazodone Placebo
Drowsiness 41% 20%
Dry mouth 34% 20%
Dizzy / Lightheaded 28% 15%
Headache 20% 16%
Blurred vision 15% 4%
Nausea 13% 10%
Decreased libido 1.3% < 1%
Other - incidence not well-defined
  • Orthostatic hypotension
  • Priapism (erection lasting > 6 hours)


Drug interactions


Contraindications / Precautions

  • Seizure - may increase risk
  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Prolonged QT syndrome - may worsen QT prolongation
  • Abnormal bleeding - through platelet inhibition
  • Low sodium (hyponatremia) - may cause SIADH
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease - use caution
  • Kidney disease - use caution

Vilazodone (Viibryd®)

Dosage forms

Tablet
  • 10 mg
  • 20 mg
  • 40 mg
Starter kit:
  • 10 mg X 7
  • 20 mg X 7
  • 40 mg X 16

Dosing

Depression
  • Starting: 10 mg once daily for 7 days, then 20 mg once daily for 7 days, then 40 mg once daily
  • Maintenance: 40 mg once daily
  • Max: 40 mg once daily
  • Take with food. Food increases absorption.
When taken with CYP3A4 strong inhibitors
  • Dose should not exceed 20 mg a day
When taken with CYP3A4 moderate inhibitors
  • Dose should not exceed 20 mg a day in patients with significant side effects
When taken with CYP3A4 strong inducers
  • Consider doubling the dose
  • Viibryd® dose should not exceed 80 mg/day

Generic / Price

- NO/$$$$

Mechanism of action

  • Serotonin modulator
  • Blocks postsynaptic serotonin receptors and inhibits postsynaptic serotonin reuptake

FDA-approved indications

- Depression

Side effects



Side effect Vilazodone Placebo
Diarrhea 28% 9%
Nausea 23% 5%
Dizziness 9% 5%
Dry mouth 8% 5%
Insomnia 6% 2%
Decreased libido 4% < 1%
Delayed ejaculation 2% 0%


Drug interactions


Contraindications / Precautions

  • Seizure - may increase risk
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Low sodium (hyponatremia) - may cause SIADH
  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Abnormal bleeding - through platelet inhibition
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease
    • Mild-moderate (Child-Pugh A/B): no dose adjustment necessary
    • Severe (Child-Pugh C): has not been studied
  • Kidney disease - no dose adjustment necessary



Mirtazapine | Remeron® | Remeron Soltab®

Dosage forms

Remeron® tablet
  • 7.5 mg
  • 15 mg
  • 30 mg
  • 45 mg
Remeron Soltab® orally disintegrating tablet
  • 15 mg
  • 30 mg
  • 45 mg

Dosing

Depression
  • Starting: 15 mg once daily at bedtime
  • Maintenance: 15 - 45 mg once daily at bedtime
  • Max: 45 mg once daily
  • Increase dose at intervals of no less than 1 - 2 weeks
  • May take without regard to food

Generic / Price

- YES/$ (tablet and ODT)

Other

Soltabs®
  • Soltabs® are placed on tongue where they dissolve and are swallowed. Water is not necessary.
  • Do not break Soltabs®
  • Use Soltabs® immediately after removing from blister pack. They cannot be stored.

Mechanism of action

  • Blocks alpha-2 adrenergic receptors which increases norepinephrine and serotonin activity
  • Blocks serotonergic 5-HT2 and 5-HT3 receptors which increases serotonergic activity
  • Blocks histamine receptors which causes sedation
  • Blocks alpha-1 receptors which may cause orthostatic hypotension
  • Blocks muscarinic receptors (anticholinergic effects)

FDA-approved indications

- Depression

Side effects



Side effect Mirtazapine Placebo
Somnolence 54% 18%
Dry mouth 25% 15%
Increased appetite 17% 2%
Elevated cholesterol / triglycerides 15% 7%
Constipation 13% 7%
Weight gain 12% 2%
Dizziness 7% 3%
Elevated liver enzymes 2% 0.3%
  • Sexual side effects are comparable to placebo in trials
  • Orthostatic hypotension may occur


Drug interactions


Contraindications / Precautions

  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Seizure - possible increase risk
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Low white blood cells - agranulocytosis has occurred in rare cases in patients taking mirtazapine
  • Low sodium (hyponatremia) - may cause SIADH
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease - clearance is decreased. No specific recommendations given. Use caution.
  • Kidney disease
    • CrCl 11 - 39 ml/min: clearance is decreased 30%
    • CrCl < 10 ml/min: clearance is decreased 50%; use caution

Vortioxetine (Trintellix®)

Dosage forms

Tablet
  • 5 mg
  • 10 mg
  • 15 mg
  • 20 mg

Dosing

Depression
  • Starting: 10 mg once daily
  • Maintenance: 20 mg once daily
  • Max: 20 mg once daily
  • May take without regard to food
When taken with CYP2D6 strong inhibitors
  • Reduce dose by half
CYP2D6 poor metabolizers
  • Maximum dose is 10 mg once daily
When taken with CYP3A4 strong inducers
  • Consider increasing the dose
  • Dose should not exceed three times the original dose

Generic / Price

- NO/$$$$

Other

  • Brand name was changed from Brintellix to Trintellix in 2016 to avoid confusion with Brilinta

Mechanism of action

  • Serotonin Reuptake Inhibitor
  • 5-HT3 receptor antagonist
  • 5-HT1A receptor agonist

FDA-approved indications

- Depression

Side effects



Side effect Vortioxetine Placebo
Nausea 32% 9%
Dizziness 9% 6%
Dry mouth 8% 6%
Constipation 8% 3%
Sexual dysfunction 5% 2%


Drug interactions


Contraindications / Precautions

  • CYP2D6 poor metabolizers - maximum dose is 10 mg once daily
  • Serotonin syndrome - may increase risk for serotonin syndrome
  • Seizure - possible increase risk
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis, angioedema, and urticaria have been reported
  • Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma
  • Suicide - possible increase in risk when starting therapy in patients ≤ 24 years old
  • Bipolar - may precipitate mania in bipolar patients
  • Abnormal bleeding - through platelet inhibition
  • Low sodium (hyponatremia) - may cause SIADH
  • Abrupt discontinuation - anxiety, confusion, paresthesias, etc.
  • Liver disease
    • Mild-moderate (Child-Pugh A/B): no dose adjustment necessary
    • Severe (Child-Pugh C): has not been studied
  • Kidney disease - no dose adjustment necessary



Pregnancy safety studies

Association Between Serotonergic Antidepressant Use During Pregnancy and Autism Spectrum Disorder in Children - JAMA (2017) [PMID 28418480]
  • Design: Retrospective cohort study (N=35,906 pregnancies)
  • Exposure: Serotonergic antidepressant exposure defined as 2 or more consecutive maternal prescriptions for an SSRI or SNRI between conception and delivery
  • Primary outcome: Child autism spectrum disorder identified after the age of 2 years
  • Findings: In children born to mothers receiving public drug coverage in Ontario, Canada, in utero serotonergic antidepressant exposure compared with no exposure was not associated with autism spectrum disorder in the child. Although a causal relationship cannot be ruled out, the previously observed association may be explained by other factors.

Associations of Maternal Antidepressant Use During the First Trimester of Pregnancy With Preterm Birth, Small for Gestational Age, Autism Spectrum Disorder, and Attention-Deficit/Hyperactivity Disorder in Offspring - JAMA (2017) [PMID 28418479]
  • Design: Retrospective cohort study (N=1,508,629 offspring)
  • Exposure: Maternal self-reported first-trimester antidepressant use and first-trimester antidepressant dispensations
  • Primary outcome: Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 SDs below the mean for gestational age), and first inpatient or outpatient clinical diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder in offspring
  • Findings: Among offspring born in Sweden, after accounting for confounding factors, first-trimester exposure to antidepressants, compared with no exposure, was associated with a small increased risk of preterm birth but no increased risk of small for gestational age, autism spectrum disorder, or attention-deficit/hyperactivity disorder

Neonatal Morbidity After Maternal Use of Antidepressant Drugs During Pregnancy. (Pediatrics 2016) [PubMed abstract]
  • Design: Cohort registry study
  • Results: Maternal use of antidepressants during pregnancy was associated with increased neonatal morbidity and a higher rate of admissions to the NICU. The absolute risk for severe disease was low, however.

Association of SSRI Exposure During Pregnancy With Speech, Scholastic, and Motor Disorders in Offspring. (JAMA Psychiatry 2016) [PubMed abstract]
  • Design: Cohort registry study
  • Results: Exposure to SSRIs during pregnancy was associated with an increased risk of speech/language disorders. This finding may have implications for understanding associations between SSRIs and child development.

Pregnancy Complications Following Prenatal Exposure to SSRIs or Maternal Psychiatric Disorders (Am J Psychiatry 2015) [PubMed abstract]
  • Design: Cohort registry study
  • Results: In a large national birth cohort, treatment of maternal psychiatric disorders with SSRIs during pregnancy was related to a lower risk of preterm birth and cesarean section but a higher risk of neonatal maladaptation. The findings provide novel evidence for a protective role of SSRIs on some deleterious reproductive outcomes, possibly by reducing maternal depressive symptoms. The divergent findings suggest that clinical decisions on SSRI use during pregnancy should be individualized, taking into account the mother's psychiatric and reproductive history.

Specific SSRIs and birth defects: Bayesian analysis to interpret new data in the context of previous reports. (BMJ 2015) [PubMed abstract]
  • Design: Bayesian case-control study
  • Results: These data provide reassuring evidence for some SSRIs but suggest that some birth defects occur 2 - 3.5 times more frequently among the infants of women treated with paroxetine or fluoxetine early in pregnancy.

Antidepressant use late in pregnancy and risk of Persistent Pulmonary Hypertension of the Newborn (PPHN) (JAMA 2015) [PubMed abstract]
  • Design: Cohort registry study
  • Results: Evidence from this large study of publicly insured pregnant women may be consistent with a potential increased risk of PPHN associated with maternal use of SSRIs in late pregnancy. However, the absolute risk was small, and the risk increase appears more modest than suggested in previous studies.

SSRIs and venlafaxine in early pregnancy and risk of birth defects (BMJ 2015) [PubMed abstract]
  • Design: Cohort registry study
  • Results: In this large Nordic study no substantial increase was found in prevalence of overall cardiac birth defects among infants exposed to SSRIs or venlafaxine in utero. Although the prevalence of septal defects and right ventricular outflow tract defects was higher in exposed infants, the lack of an association in the sibling controlled analyses points against a teratogenic effect of these drugs.

Tamoxifen interaction studies

Risk of mortality with concomitant use of tamoxifen and SSRIs: multi-database cohort study. (BMJ 2016) [PubMed abstract]
  • Design: Retrospective registry cohort study (N=14,532 | length = median 2.2 years) in women with breast cancer taking tamoxifen and SSRIs
  • Exposure: Potent CYP2D6 Inhibitors (paroxetine and fluoxetine) vs Other SSRIs
  • Primary outcome: All cause mortality in each cohort in women taking SSRIs that are potent inhibitors of CYP2D6 (paroxetine, fluoxetine) versus other SSRIs
  • Findings: Concomitant use of tamoxifen and potent CYP2D6 inhibiting SSRIs versus other SSRIs was not associated with an increased risk of death

Tamoxifen and Antidepressant Drug Interaction in a Cohort of 16,887 Breast Cancer Survivors (J Natl Cancer Inst 2015) [PubMed abstract]
  • Design: Retrospective registry cohort study (N=16,887 | length = median 6 years) in breast cancer survivors
  • Exposure: Tamoxifen + Antidepressant vs Tamoxifen and no Antidepressant
  • Primary outcome: Risk of subsequent breast cancer
  • Results: Using the comprehensive electronic health records of insured patients, we did not observe an increased risk of subsequent breast cancer in women who concurrently used tamoxifen and antidepressants, including paroxetine

Resistant depression studies

Switch to Bupropion vs Add Bupropion vs Add Antipsychotic in Resistant MDD, JAMA (2017) [PubMed abstract]
  • Design: Randomized, controlled trial (N=1522, length = 12 weeks) in patients with MDD who were failing SSRI, SNRI, or mirtazapine therapy
  • Treatment: Switch to Bupropion 300 - 400 mg/day vs Add Bupropion 300 - 400 mg/day vs Add aripiprazole 5 - 15 mg/day
  • Primary outcome: Remission during the acute treatment phase of 12 weeks
  • Results:
    • Primary outcome: Switch to bupropion - 22%, Add bupropion - 27%, Add aripiprazole - 29% (add aripiprazole vs switch to bupropion p=0.02)
  • Findings: Among a predominantly male population with MDD unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach.

Addition of Aripiprazole vs Placebo to MDD resistant to Venlafaxine (Lancet 2015) [PubMed abstract]
  • Design: Randomized, controlled trial (N=468, length = 12 weeks) in adults older than 60 with MDD who were failing venlafaxine 150 - 300 mg/day
  • Treatment: Aripiprazole (target dose 10 mg/day) vs Placebo
  • Primary outcome: Remission (defined as an MADRS score of ≤ 10 and at least 2 points below the score at the start of the randomised phase) at both of the final two consecutive visits
  • Results:
    • Primary outcome: Aripiprazole - 44%, Placebo - 29% (p=0.03)
  • Findings: In adults aged 60 years or older who do not achieve remission from depression with a first-line antidepressant, the addition of aripiprazole is effective in achieving and sustaining remission. Tolerability concerns include the potential for akathisia and Parkinsonism.

Antidepressant vs placebo studies

Escitalopram vs Placebo in Patients with Acute Coronary Syndrome and Depression, JAMA (2018) [PubMed abstract]
  • Design: Randomized, placebo-controlled trial (N=300, length = 24 weeks) in patients with acute coronary syndrome and depression
  • Treatment: Escitalopram 5 - 20 mg/day vs Placebo
  • Primary outcome: A composite of all-cause mortality, myocardial infarction (MI), and percutaneous coronary intervention (PCI)
  • Results:
    • Primary outcome: Escitalopram - 41%, Placebo - 53.6% (p=0.03)
  • Findings: Among patients with depression following recent acute coronary syndrome, 24-week treatment with escitalopram compared with placebo resulted in a lower risk of major adverse cardiac events after a median of 8.1 years. Further research is needed to assess the generalizability of these findings.

Escitalopram vs Placebo in Patients with Heart Failure and Depression , JAMA (2016) [PubMed abstract]
  • Design: Randomized, placebo-controlled trial (N=372, length = 24 months) in patients with heart failure and depression
  • Treatment: Escitalopram 10 - 20 mg/day vs Placebo
  • Primary outcome: Composite of time to all-cause death or hospitalization
  • Results:
    • Primary outcome: Escitalopram - 63%, Placebo - 64% (p=0.92)
  • Findings: In patients with chronic heart failure with reduced ejection fraction and depression, 18 months of treatment with escitalopram compared with placebo did not significantly reduce all-cause mortality or hospitalization, and there was no significant improvement in depression. These findings do not support the use of escitalopram in patients with chronic systolic heart failure and depression.

Sertraline vs Placebo in Patients with Chronic Kidney Disease and Depression, JAMA (2017) [PubMed abstract]
  • Design: Randomized, placebo-controlled trial (N=201, length = 12 weeks) in patients with chronic kidney disease and depression
  • Treatment: Sertraline 50 - 200 mg/day vs Placebo
  • Primary outcome: Improvement in depressive symptom severity from baseline to 12 weeks
  • Results:
    • Primary outcome (change in score): Sertraline -4.1, Placebo -4.2 (p=0.82)
  • Findings: Among patients with non-dialysis-dependent CKD and MDD, treatment with sertraline compared with placebo for 12 weeks did not significantly improve depressive symptoms. These findings do not support the use of sertraline to treat MDD in patients with non-dialysis-dependent CKD.

Fluoxetine vs Placebo for Functional Outcomes after Acute Stroke, Lancet (2019) [PubMed abstract]
  • Design: Randomized, placebo-controlled trial (N=3127 | length = 12 months) in patients with acute stroke and focal neurological deficit at the time of randomisation
  • Treatment: Fluoxetine 20 mg once daily vs Placebo for 6 months
  • Primary outcome: Functional status, measured with the modified Rankin Scale (mRS), at 6 months
  • Results:
    • Primary outcome: The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (p=0.44)
  • Findings: Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function

Smoking cessation studies

Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders, Lancet (2016) [PubMed abstract]
  • Design: Randomized placebo-controlled trial (N=8144, length=24 weeks)
  • Treatment: Nicotine patch vs Varenicline vs Bupropion vs Placebo
  • Primary outcome: 1. Incidence of a composite measure of moderate and severe neuropsychiatric adverse events 2. Biochemically confirmed continuous abstinence for weeks 9 - 12
  • Results:
    • Primary outcome (neuropsychiatric events in nonpsychiatric cohort): Varenicline - 1.3%, Bupropion - 2.2%, Nicotine patch - 2.5%, Placebo - 2.4%
    • Primary outcome (neuropsychiatric events in psychiatric cohort): Varenicline - 6.5%, Bupropion - 6.7%, Nicotine patch - 5.2%, Placebo - 4.9%
    • Primary outcome (tobacco abstinence weeks 9 - 12): Varenicline - 33.5%, Bupropion - 22.6%, Nicotine patch - 23.4%, Placebo - 12.5%
  • Findings:The study did not show a significant increase in neuropsychiatric adverse events attributable to varenicline or bupropion relative to nicotine patch or placebo. Varenicline was more effective than placebo, nicotine patch, and bupropion in helping smokers achieve abstinence, whereas bupropion and nicotine patch were more effective than placebo.

Amitriptyline vs Topiramate vs Placebo for Prevention of Pediatric Migraine, NEJM (2017) [PubMed abstract]
  • The trial enrolled children 8 to 17 years old with ≥ 4 migraines/month
Main inclusion criteria
  • Females or males 8 - 17 years
  • Migraine with or without aura or chronic migraine
  • ≥ 4 migraine days a month
Main exclusion criteria
  • Current use of preventive migraine med
  • Previously failed amitriptyline or topiramate
  • Prolonged QT interval (≥ 450 msec)
Baseline characteristics
  • Average age - 14 years
  • Average # of headache days/month - 11
  • Female sex - 69%
Randomized treatment groups
  • Group 1 (144 patients): Amitriptyline target dose of 1 mg/kg/day given in 2 divided doses
  • Group 2 (145 patients): Topiramate target dose of 2 mg/kg/day given in 2 divided doses
  • Group 3 (72 patients): Placebo
  • Doses were increased every 2 weeks over 8 weeks
  • The trial had a 28-day baseline period before randomization
Primary outcome: Relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with the last 28 days of a 24-week trial
Results

Duration: 24 weeks
Outcome Group 1 Group 2 Group 3 Comparisons
Primary outcome 52% 55% 61% 1 vs 3: p=0.26 | 2 vs 3: p=0.48
Reduction in headache days/month 6.7 6.7 5.9 1 vs 3: p=0.36 | 2 vs 3: p=0.41

Findings: There were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent migraine with amitriptyline, topiramate, or placebo over a period of 24 weeks. The active drugs were associated with higher rates of adverse events.



Pricing legend
  • $ = 0 - $50
  • $$ = $51 - $100
  • $$$ = $101 - $150
  • $$$$ = > $151
  • Pricing based on one month of therapy at standard dosing in an adult
  • Pricing based on information from GoodRX.com®
  • Pricing may vary by region and availability