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• Selective Serotonin Reuptake Inhibitors (SSRI)

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Citalopram (Celexa®)	Citalopram tablet 10mg 20mg 40mg	Depression Starting - 20mg a day Maintenance - 20 - 40mg a day Max - 40mg a day Max dose of 20mg a day recommended for patients > 60 years old, and patients with liver disease Poor CYP2C19 metabolizers, and patients taking CYP2C19 inhibitors Maximum daily dose is 20 mg See CYP2C19 for more	Citalopram YES/$	May take without regard to food	SSRI Inhibits serotonin reuptake by neurons	Depression	Nausea- 21%, P - 14% Dry mouth - 20%, P - 14% Somnolence- 18%, P - 10% Insomnia- 15%, P - 14% Increased sweating - 11%, P - 9% Ejaculation disorder - 6%, P - 1%	MAO inhibitors - DO NOT COMBINE Pimozide (Orap®) - DO NOT COMBINE Drugs that prolong the QT interval - DO NOT COMBINE Serotonergic drugs - may increase risk of serotonin syndrome Anticoagulant/Antiplatelet meds - may increase bleeding risk CYP2C19 inhibitors - may increase citalopram levels. Maximum citalopram dose is 20mg a day.	Prolonged QT syndrome - citalopram should be stopped in patients with persistent QTc longer than 500ms 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 20mg a day Liver disease - maximum dose is 20mg a day Kidney disease CrCl ≥ 30 ml/min: no dose adjustment necessary CrCl < 30 ml/min: use caution

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Escitalopram (Lexapro®)	Escitalopram tablet 5mg 10mg 20mg	Depression/Generalized anxiety disorder Starting - 10mg once daily Maintenance - 10 - 20mg once daily Max - 20mg once daily Liver disease - 10mg once daily Elderly - 10mg once daily Increase dose after a minimum of one week	Escitalopram YES/$	May take without regard to food	SSRI Inhibits serotonin reuptake by neurons	Depression Generalized anxiety disorder	Nausea- 15%, P - 7% Insomnia- 9%, P - 4% Ejaculation disorder (delay) - 9%, P - <1% Diarrhea - 8%, P - 5% Somnolence- 6%, P - 2%	MAO inhibitors - DO NOT COMBINE Pimozide (Orap®) - DO NOT COMBINE Drugs that prolong the QT interval Serotonergic drugs - may increase risk of serotonin syndrome Anticoagulant/Antiplatelet meds - may increase bleeding risk CYP2D6 substrates - escitalopram is a weak CYP2D6 inhibitor	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 10mg a day Kidney disease CrCl ≥ 30 ml/min: no dose adjustment necessary CrCl < 30 ml/min: use caution

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Fluoxetine (Prozac®) (Prozac weekly™) (Sarafem®) Fluoxetine + olanzapine (Symbyax®)	Fluoxetine capsule 10mg 20mg 40mg Fluoxetine tablet 10mg 20mg 60mg Prozac Weekly® 90mg capsule Sarafem® tablet 10mg 15mg 20mg Symbyax® capsule Fluoxetine(mg):Olanzapine(mg) 25:3 25:6 25:12 50:6 50:12 NOTE: see also olanzapine	Fluoxetine (Prozac®)  Depression Starting - 20mg once daily Maintenance - 20 - 40mg once daily Max - 80mg once daily Obsessive compulsive disorder Starting - 20mg once daily Maintenance - 20 - 60mg once daily Max - 80mg once daily Bulimia nervosa Target dose - 60mg once daily Max - 60mg once daily In trials, only the 60mg dose was superior to placebo Panic disorder Starting - 10mg once daily Maintenance - 10 - 60mg once daily Max - 60mg once daily Prozac weekly® Depression 90mg once a week Sarafem® Premenstrual dysphoric disorder Continuous dosing: 20mg once daily Intermittent dosing: 20mg once daily starting 14 days before menstruation through first full day of menses Fluoxetine + olanzapine (Symbyax®) Depression associated with Bipolar 1 and Treatment resistant depression Starting - 25/6mg once daily in the evening Maintenance - 25/6mg - 50/18mg once daily Max - 75/18mg once daily NOTE: see also olanzapine	Prozac® YES/$ Prozac weekly™ YES/$$-$$$ Sarafem­ NO/$$$$ Symbyax™ YES/$$$$	May take without regard to food 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	SSRI Inhibits serotonin reuptake by neurons	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 NOTE: see also olanzapine	Nausea - 22%, P - 9% Headache- 21%, P - 19% Insomnia- 19%, P - 10% Nervousness- 13%, P - 8% Fatigue- 11%, P - 6% Diarrhea- 11%, P - 7% Decreased appetite - 10%, P - 3% Abnormal ejaculation - 7%, P - 1%	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.	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

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Fluvoxamine (Luvox®) (Luvox® CR)	Luvox® tablet 25mg 50mg 100mg Luvox CR® capsule 100mg 150mg	Depression Luvox® Starting - 50mg once daily at bedtime Maintenance - 100 - 300mg a day Max - 300mg a day Doses > 100mg should be given in 2 divided doses Increase in increments of 50mg/day every 4 - 7 days Luvox® CR Starting - 100mg once daily at bedtime Maintenance - 100 - 300mg once daily Max - 300mg once daily Increase in increments of 50mg/day every 7 days	Luvox® YES/$ Luvox® CR YES/$$$$	May take without regard to food Because of the potential for drug interactions, fluvoxamine is not widely used	SSRI Inhibits serotonin reuptake by neurons	Obsessive-Compulsive Disorder (OCD)	Nausea - 40%, P - 14% Somnolence- 22%, P - 8% Headache- 22%, P - 20% Insomnia- 21%, P - 10% Fatigue- 14%, P - 6% Dry mouth - 14%, P - 10% Nervousness- 12%, P - 5% Dizziness- 11%, P - 6% Diarrhea- 11%, P - 7% Delayed ejaculation - 8%, P - 1%	Alosetron (Lotronex®) - DO NOT COMBINE MAO inhibitors - DO NOT COMBINE Pimozide (Orap®) - DO NOT COMBINE Thioridazine - DO NOT COMBINE Tizanidine (Zanaflex®) - DO NOT COMBINE Drugs that prolong the QT interval Serotonergic drugs - may increase risk of serotonin syndrome Anticoagulant/Antiplatelet meds - may increase bleeding risk CYP1A2 substrates - fluvoxamine is a strong CYP1A2 inhibitor CYP3A4 substrates - fluvoxamine is a strong CYP3A4 inhibitor CYP2C19 substrates - fluvoxamine is a strong CYP2C19 inhibitor CYP2C9 substrates - fluvoxamine is a moderate CYP2C9 inhibitor	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

Drug	Dosage form	Dosage		Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Paroxetine (Paxil®) (Paxil CR®) (Brisdelle™) (Pexeva®)	Paxil® (paroxetine HCL) tablet 10mg 20mg 30mg 40mg Paxil CR® (paroxetine HCL) tablet 12.5mg 25mg 37.5mg Pexeva® (paroxetine mesylate) tablet 10mg 20mg 30mg 40mg Brisdelle™ (paroxetine mesylate) 7.5mg	Depression Paxil®, Pexeva® Starting - 20mg once daily Maintenance - 20 - 50mg once daily Max - 50mg once daily Increase in increments of 10mg/day every 7 days Liver and kidney disease - initial dose 10mg a day. Do not exceed 40mg a day. Paxil CR® Starting - 25mg once daily Maintenance - 25 - 62.5mg once daily Max - 62.5mg once daily Increase in increments of 12.5mg/day every 7 days Liver and kidney disease - initial dose 12.5mg a day. Do not exceed 50mg a day. Obsessive compulsive disorder (OCD) Paxil®, Pexeva® Starting - 20mg once daily Target - 40mg once daily Max - 60mg once daily Increase in increments of 10mg/day every 7 days Panic disorder Paxil®, Pexeva® Starting - 10mg once daily Target - 40mg once daily Max - 60mg once daily Increase in increments of 10mg/day every 7 days Paxil CR® Starting - 12.5mg once daily Maintenance - 12.5 - 75mg once daily Max - 75mg once daily Increase in increments of 12.5mg/day every 7 days	Social anxiety disorder Paxil® Starting - 20mg once daily Maintenance - 20 - 60mg once daily Max - 60mg once daily Increase in increments of 10mg/day every 7 days Paxil CR® Starting - 12.5mg once daily Maintenance - 12.5 - 37.5mg once daily Max - 37.5mg once daily Increase in increments of 12.5mg/day every 7 days Generalized anxiety disorder Paxil®, Pexeva® Starting - 20mg once daily Target - 20 once daily Max - 50mg once daily Increase in increments of 10mg/day every 7 days Posttraumatic stress disorder Paxil® Starting - 20mg once daily Target - 20 once daily Max - 50mg once daily Increase in increments of 10mg/day every 7 days Premenstrual dysphoric disorder Paxil CR® Continuous - 12.5 - 25mg once daily Intermittent - 12.5 - 25mg once daily during the luteal phase (days 14 - 28 of the menstrual cycle with day 1 being the first day of menses) Vasomotor symptoms associated with menopause Brisdelle™ 7.5mg once daily at bedtime	Paxil® YES/$ Paxil® CR YES/$$-$$$ Pexeva® NO/$$$$ Brisdelle™ NO/$$$-$$$$	All May take without regard to food Paxil® CR Do not crush or chew tablet	SSRI Inhibits serotonin reuptake by neurons	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	Nausea- 26%, P - 9% Somnolence- 23%, P - 9% Headache- 18%, P - 17% Dry Mouth - 18%, P - 12% Fatigue- 15%, P - 6% Constipation- 14%, P - 9% Dizziness- 13%, P - 6% Insomnia- 13%, P - 6% Ejaculatory delay - 13%, P - 0% Diarrhea- 12%, P - 8% Sweating- 11%, P - 2% Other male sexual dysfunction - 10%, P - 0%	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 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.	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

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Sertraline (Zoloft®)	Zoloft® 25mg 50mg 100mg	Depression and Obsessive compulsive disorder Starting - 50mg once daily Maintenance - 50 - 200mg once daily Max - 200mg once daily Increase dose at intervals of ≥ 1 week Panic disorder, Posttraumatic stress disorder (PTSD), Social anxiety disorder Starting - 25mg once daily Maintenance - 50 - 200mg once daily Max - 200mg a day Increase dose at intervals of ≥ 1 week Premenstrual dysphoric disorder Continuous - 50 - 150mg once daily Intermittent - 50 - 100mg once daily during the luteal phase (days 14 - 28 of the menstrual cycle with day 1 being the first day of menses) Increase dose at the onset of each new cycle For 100mg/day intermittent dosing, use 50mg/day for first 3 days of each new cycle	Zoloft® YES/$	May take without regard to food	Selective Serotonin Reuptake Inhibitor (SSRI) Inhibits serotonin reuptake by neurons	Depression Obsessive-Compulsive Disorder (OCD) Panic disorder Posttraumatic Stress Disorder (PTSD) Premenstrual Dysphoric Disorder Social Anxiety Disorder	Nausea- 25%, P - 11% Headache- 25%, P - 23% Insomnia- 21%, P - 11% Diarrhea- 20%, P - 10% Ejaculation failure - 14%, P - 1% Dry Mouth - 14%, P - 8% Somnolence- 13%, P - 7% Dizziness- 12%, P - 7% Fatigue- 12%, P - 7%	MAO inhibitors - DO NOT COMBINE Pimozide (Orap®) - DO NOT COMBINE Drugs that prolong the QT interval Warfarin (Coumadin®) - may increase effect of warfarin Carbamazepine (Tegretol®) - may reduce sertraline levels Cimetidine (Tagamet®) - may increase sertraline levels Serotonergic drugs - may increase risk of serotonin syndrome Anticoagulant/Antiplatelet meds - may increase bleeding risk CYP2D6 substrates - sertraline is a weak CYP2D6 inhibitor	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

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• Serotonin-Norepinephrine Reuptake Inhibitor (SNRIs)

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Desvenlafaxine Succinate (Pristiq®) Desvenlafaxine (Khedezla™)	Pristiq® extended-release tablet 25mg 50mg 100mg Khedezla™ extended-release tablet 50mg 100mg	Depression Pristiq®, Khedezla™ Starting - 50mg once daily Maintenance - 50 - 400mg once daily Max - 400mg once daily	Pristiq® NO/$$$$ Khedezla™ NO/$$$	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 50mg a day	Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) Inhibits serotonin and norepinephrine reuptake by neurons	Depression	Nausea- 26%, P - 10% Dry Mouth - 17%, P - 9% Insomnia- 12%, P - 6% Sweating- 11%, P - 4% Dizziness- 10%, P - 5% Constipation- 9%, P - 4% Ejaculation delay - 5%, P - < 1% Erectile dysfunction - 6%, P - 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) NOTE: Side effects incidence are for 100mg a day dosing	MAO inhibitors - DO NOT COMBINE Serotonergic drugs - may increase risk of serotonin syndrome Anticoagulant/Antiplatelet meds - may increase bleeding risk CYP2D6 substrates - desvenlafaxine is a weak CYP2D6 inhibitor. When taking desvenlafaxine 400mg 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.	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 Abrupt discontinuation - anxiety, confusion, paresthesias, etc. Liver disease Moderate-severe disease (Child-Pugh B and C): - recommended dose is 50mg a day; do not exceed 100mg a day Kidney disease CrCl 30 - 50 ml/min: max dose is 50mg a day CrCl < 30 ml/min: max dose is 50mg every other day

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Duloxetine (Cymbalta®)	Cymbalta® capsule 20mg 30mg 60mg	Depression Starting - 30 - 60mg a day Maintenance - 40 - 60mg a day Max - 120mg a day May be given once daily or in two divided doses Generalized anxiety disorder Starting - 30 - 60mg once daily Maintenance - 60 - 120mg once daily Max - 120mg once daily Diabetic peripheral neuropathy Starting - 30 - 60mg once daily Target - 60mg once daily Max - 60mg once daily Fibromyalgia Starting - 30 - 60mg once daily Target - 60mg once daily Max - 60mg once daily Chronic musculoskeletal pain Starting - 30 - 60mg once daily Target - 60mg once daily Max - 60mg once daily	Cymbalta® YES/$	May take without regard to food Do not open, crush, or chew capsule In most studies, doses > 60mg a day have not shown additional benefit	Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) Inhibits serotonin and norepinephrine reuptake by neurons	Depression Generalized anxiety disorder Diabetic peripheral neuropathy Fibromyalgia Chronic musculoskeletal pain	Nausea- 23%, P - 8% Dry Mouth - 14%, P - 6% Headache- 14%, P - 14% Constipation- 9%, P - 4% Diarrhea- 9%, P - 6% Fatigue- 9%, P - 5% Somnolence- 9%, P - 3% Insomnia- 9%, P - 5% Erectile dysfunction - 4%, P - 1% Ejaculation delay - 2%, P - 1% Elevated liver enzymes (> 3X upper limit of normal) - 1.25%, P - 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	MAO inhibitors - DO NOT COMBINE Thioridazine - DO NOT COMBINE CYP1A2 strong inhibitors - DO NOT COMBINE Serotonergic drugs - may increase risk of serotonin syndrome CYP2D6 strong inhibitors - may increase duloxetine levels CYP2D6 substrates - duloxetine is a moderate CYP2D6 inhibitor. It may increase CYP2D6 substrate levels. Anticoagulant/Antiplatelet meds - may increase bleeding risk	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

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Levomilnacipran (Fetzima™)	Fetzima™ extended-release capsule 20mg 40mg 80mg 120mg Titration pack: 20mg capsule X 2 40mg capsule X 26	Depression Starting - 20mg once daily for 2 days, then 40mg once daily Maintenance - 40 - 120mg once daily Max - 120mg once daily Increase in increments of 40mg/day at intervals of ≥ 2 days Dosing in kidney disease CrCl ≥ 60 ml/min: no dose adjustment necessary CrCl 30 - 59 ml/min: do not exceed 80mg a day CrCl 15 - 29 ml/min: do not exceed 40mg/day CrCl < 15 ml/min: not recommended Dosing with strong CYP3A4 inhibitors Do not exceed 80mg a day	Fetzima™ NO/$$$$	May take without regard to food Do not open, chew, or crush capsule	Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) Inhibits serotonin and norepinephrine reuptake by neurons	Depression	Nausea - 17%, P - 6% Constipation - 9%, P - 3% Excessive sweating - 9%, P - 2% Erectile dysfunction - 6%, P - 1% Rapid heart beat - 6%, P - 2% Urinary hesitancy/retention - 5%, P - 0% Ejaculation disorder - 5%, P - <1% Vomiting - 5%, P - 1% Palpitations - 5%, P - 1% Testicular pain - 4%, P - <1% Hot flush - 3%, P - 1% Orthostatic hypotension - 3%, P - 1% Decreased appetite - 3%, P - 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	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 80mg a day when taken with CYP3A4 strong inhibitors Serotonergic drugs - may increase risk of serotonin syndrome Anticoagulant/Antiplatelet meds - may increase bleeding risk	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 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 - See Dosage

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Venlafaxine (Effexor®) (Effexor XR®)	Effexor® tablet 25mg 37.5mg 50mg 75mg 100mg Effexor XR® extended-release capsule 37.5mg 75mg 150mg Effexor XR® extended-release tablet 37.5mg 75mg 150mg 225mg	Depression Effexor® Starting - 75mg a day Maintenance - 75 - 225mg a day Max - 375mg a day Give in 2 to 3 divided doses Increase dose in increments of up to 75mg/day at intervals of ≥ 4 days Doses higher than 225mg a day have not been extensively studied Effexor XR® Starting - 37.5 - 75mg once daily Maintenance - 75 - 225mg once daily Max - 225mg once daily Increase dose in increments of up to 75mg/day at intervals of ≥ 4 days Generalized anxiety disorder Effexor XR® Starting - 37.5 - 75mg once daily Maintenance - 75 - 225mg once daily Max - 225mg once daily Increase dose in increments of up to 75mg/day at intervals of ≥ 4 days Social anxiety disorder Effexor XR® Target - 75mg once daily There is no evidence that higher doses are beneficial Panic disorder Effexor XR® Starting - 37.5 once daily Maintenance - 75 - 225mg once daily Max - 225mg once daily Increase dose in increments of up to 75mg/day at intervals of ≥ 7 days Migraine prevention (off-label) Effexor XR® 75 - 150 mg/day Diabetic neuropathy (off-label) Starting: 37.5 mg once daily Target: 75 - 225 mg/day See diabetic neuropathy for more	Effexor® YES/$ Effexor XR® YES/ capsule - $ tablet - $$-$$$	Effexor® Take with food to help reduce nausea May cause false-positive urine drug tests for phencyclidine (PCP) and amphetamines Effexor XR® Take with food to help reduce nausea 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	Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) Inhibits serotonin and norepinephrine reuptake by neurons Weak dopamine reuptake inhibitor	Depression Generalized anxiety disorder Social anxiety disorder Panic disorder	Nausea- 35%, P - 12% Dizziness- 16%, P - 11% Dry Mouth - 16%, P - 6% Insomnia- 15%, P - 10% Somnolence- 14%, P - 8% Fatigue- 12%, P - 8% Ejaculation delay/abnormal - 11%, P - < 1% Constipation- 10%, P - 4% Sweating- 10%, P - 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)	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 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	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

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• Norepinephrine-dopamine reuptake inhibitors

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Bupropion (Wellbutrin®) (Wellbutrin SR®) (Wellbutrin XL®) (Zyban®) (Aplenzin®) (Forfivo XL™) (Contrave®)	Wellbutrin® tablet 75mg 100mg Wellbutrin SR® tablet 100mg 150mg 200mg Wellbutrin XL® tablet 150mg 300mg Forfivo XL™ tablet 450mg Zyban® tablet 150mg Aplenzin® (Bupropion hydrobromide) tablet 174mg 348mg 522mg Contrave® (naltrexone + bupropion) see Contrave®	Depression Wellbutrin® Starting - 100mg twice a day for 3 days Maintenance - 100mg three times a day Max - 450mg a day Wellbutrin SR® Starting - 150mg once a day for 3 days Maintenance - 150mg twice a day Max - 200mg twice a day Wellbutrin XL® Starting - 150mg once daily Maintenance - 300mg once daily Max - 450mg once daily Increase dose at intervals ≥ 4 days Aplenzin® Starting - 174mg once daily for 4 days Maintenance - 348mg once daily Max - 522mg once daily Aplenzin-Wellbutrin XL equivalence: 174mg = 150mg, 348mg = 300mg, 522 = 450mg Forfivo XL™ Starting - use another form of bupropion to initiate therapy Maintenance - 450mg once daily Max - 450mg once daily Seasonal affective disorder  Wellbutrin XL® Starting - 150mg once daily Target - 300mg once daily Max - 300mg once daily Increase dose at intervals ≥ 7 days Aplenzin® Starting - 174mg once daily Target - 348mg once daily Max - 348mg once daily Increase dose at intervals ≥ 7 days Aplenzin-Wellbutrin XL equivalence: 174mg = 150mg, 348mg = 300mg, 522 = 450mg Smoking cessation Zyban® Starting - 150mg once daily for 3 days Maintenance - 150mg twice a day Max - 150mg twice a day Weight loss Contrave® (naltrexone + bupropion) See Contrave®	Wellbutrin® YES/$ Wellbutrin SR® YES/$ Wellbutrin XL® YES/$ Forfivo XL™ NO/$$$$ Aplenzin® NO/$$$$ Zyban® YES/$-$$	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	Norepinephrine-Dopamine Reuptake Inhibitor Inhibits norepinephrine and dopamine reuptake by neurons	Depression Seasonal affective disorder Smoking cessation	Agitation- 32%, P - 22% Dry mouth - 28%, P - 18% Constipation- 26%, P - 17% Headache- 26%, P - 22% Nausea- 23%, P - 19% Excessive sweating - 22%, P - 15% Dizziness- 22%, P - 16% Tremor- 21%, P - 8% Insomnia- 19%, P - 16% Blurred vision - 15%, P - 10% Rapid heart beat - 11%, P - 9% Increased blood pressure - may increase blood pressure. Incidence is unknown.	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.	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 higher risk of seizure. Alcohol/benzodiazepine/barbiturate withdrawal - DO NOT USE. These patients have higher risk of seizure. Antiepileptic drug withdrawal - DO NOT USE. These patients have 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 75mg a day Wellbutrin SR Mild (Child-Pugh A): consider dose/frequency reduction Moderate-severe (Child-Pugh B/C): max dose is 100mg a day or 150mg every other day Wellbutrin XL, Zyban Mild (Child-Pugh A): consider dose/frequency reduction Moderate-severe (Child-Pugh B/C): max dose is 150mg every other day Aplenzin Severe (Child-Pugh C): max dose is 174mg 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

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• Tricyclic antidepressants (TCAs)

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Amitriptyline (Elavil®)	Amitriptyline tablet 10mg 25mg 50mg 75mg 100mg 150mg	Depression Starting - 25- 50mg once daily Maintenance - 50 - 100mg once daily Max - 150mg once daily Migraine prevention (off-label) 25 - 150 mg/day Diabetic neuropathy (off-label) Starting: 10 - 25 mg once daily Target: 25 - 100 mg/day See diabetic neuropathy for more	Amitriptyline YES/$	May take without regard to food	Tricyclic antidepressant Inhibits norepinephrine and serotonin reuptake by neurons	Depression	Dry mouth - > 50% of patients in some trials Drowsiness- common Blurred vision Constipation Urinary retention Postural hypotension NOTE: Clomipramine is another TCA. It has the most extensive side effect information available. (see clomipramine below)	MAO inhibitors - DO NOT COMBINE Anticholinergic medications - may potentiate side effects Serotonergic drugs - may increase risk of serotonin syndrome Anticoagulant/Antiplatelet meds - may increase bleeding risk CYP2D6 inhibitors - may increase levels of amitriptyline CYP1A2 substrates - amitriptyline is a moderate CYP1A2 inhibitor CYP2C19 substrates - amitriptyline is a strong CYP2C19 inhibitor Topiramate - topiramate may increase amitriptyline levels Valproic acid - valproic acid may increase amitriptyline levels Clonidine - amitriptyline may decrease the effectiveness of clonidine Drugs that prolong the QT interval	Seizure - may increase risk 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

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Clomipramine (Anafranil™)	Clomipramine capsule 25mg 50mg 75mg	Obsessive compulsive disorder Starting - 25mg a day Maintenance - 100mg a day Max - 250mg a day When initiating, increase to 100mg a day over the course of 2 weeks May be given in divided doses to decrease gastrointestinal side effects	Anafranil™ YES/$$$$	Take with food to limit GI side effects Gradually increase dose. May give twice a day when initiating to limit side effects.	Tricyclic antidepressant Inhibits norepinephrine and serotonin reuptake by neurons	Obsessive-compulsive disorder (OCD)	Dry mouth - 84%, P - 17% Somnolence- 54%, P - 16% Tremor - 54%, P - 2% Dizziness- 54%, P - 14% Headache- 52%, P - 41% Constipation- 47%, P - 11% Ejaculation failure - 42%, P - 2% Nausea - 33%, P - 14% Increased sweating - 29%, P - 3% Insomnia- 25%, P - 15% Libido change - 21%, P - 3% Impotence- 20%, P - 3% Weight gain - 18%, P - 1% Abnormal vision - 18%, P - 4% Nervousness- 18%, P - 2% Urinary retention - 14%, P - 2% Diarrhea- 13%, P - 9% Myalgia - 13%, P - 9% Muscle twitching - 13%, P - 0% Increased appetite - 11%, P - 2% Orthostatic hypotension Elevated liver enzymes - 1-3% of patients	MAO inhibitors - DO NOT COMBINE Anticholinergic medications - may potentiate side effects Methylphenidate (Ritalin®, Concerta®) - may increase clomipramine levels Haloperidol (Haldol®) - may increase clomipramine levels Phenobarbital - may increase phenobarbital levels Carbamazepine - may increase clomipramine levels Anticoagulant/Antiplatelet meds - may increase bleeding risk Serotonergic drugs - may increase risk of serotonin syndrome CYP2D6 inhibitors - may increase clomipramine levels CYP1A2 inhibitors - may increase clomipramine levels CYP2C19 inhibitors and substrates - clomipramine is a CYP2C19 strong inhibitor and substrate CYP3A4 inhibitors - may increase clomipramine levels Valproic acid - valproic acid may increase clomipramine levels Clonidine - clomipramine may decrease the effectiveness of clonidine Drugs that prolong the QT interval	Seizure - may increase risk 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

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Desipramine (Norpramin®)	Desipramine tablet 10mg 25mg 50mg 75mg 100mg 150mg	Depression Starting - 50mg a day Maintenance - 100 - 200mg a day Max - 300mg a day May be given once daily or in divided doses	Desipramine YES/$$-$$$	May take without regard to food	Tricyclic antidepressant Inhibits norepinephrine and serotonin reuptake by neurons	Depression	Dry mouth - > 50% of patients in some trials Drowsiness- common Blurred vision Constipation Urinary retention Postural hypotension NOTE: Clomipramine is another TCA. It has the most extensive side effect information available. (see clomipramine above)	MAO inhibitors - DO NOT COMBINE Anticholinergic medications - may potentiate side effects Serotonergic drugs - may increase risk of serotonin syndrome Anticoagulant/Antiplatelet meds - may increase bleeding risk CYP2D6 inhibitors - may increase levels of desipramine OCT2 substrates - desipramine is an OCT2 inhibitor Clonidine - desipramine may decrease the effectiveness of clonidine Drugs that prolong the QT interval	Seizure - may increase risk 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

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Imipramine (Tofranil™) (Tofranil-PM™)	Tofranil™ tablet 10mg 25mg 50mg Tofranil-PM™ capsule 75mg 100mg 125mg 150mg	Depression Tofranil™ Starting - 75mg a day Maintenance - 50 - 150mg a day Max - 200mg a day May be given once daily or in divided doses Tofranil PM™ Starting - 75mg a day Maintenance - 75 - 150mg a day Max - 200mg a day May be given once daily or in divided doses Childhood enuresis (≥ 6 years old) Tofranil™ Starting - 25mg one hour before bedtime Maintenance: (6-11 years) 25 - 50mg at night (≥ 12 years) 25 - 75mg at night Max - 2.5mg/kg/day or 75mg a day, whichever is less For early bedwetters, a divided dose of 25mg given midafternoon and repeated at bedtime may be more effective	Tofranil™ YES/$ Tofranil PM™ YES/$$$$	May take without regard to food	Tricyclic antidepressant Inhibits norepinephrine and serotonin reuptake by neurons	Tofranil™ Depression Childhood enuresis (bedwetting) Tofranil PM™ Depression	Dry mouth - > 50% of patients in some trials Drowsiness- common Blurred vision Constipation Urinary retention Postural hypotension NOTE: Clomipramine is another TCA. It has the most extensive side effect information available. (see clomipramine above)	MAO inhibitors - DO NOT COMBINE Anticholinergic medications - may potentiate side effects Methylphenidate (Ritalin®, Concerta®) - may increase imipramine levels Serotonergic drugs - may increase risk of serotonin syndrome Anticoagulant/Antiplatelet meds - may increase bleeding risk CYP2D6 inhibitors - may increase levels of imipramine CYP2C19 substrates - imipramine is a strong CYP2C19 inhibitor CYP1A2 substrates - imipramine is a moderate CYP1A2 inhibitor OCT2 substrates - imipramine is an OCT2 inhibitor Clonidine - imipramine may decrease the effectiveness of clonidine Drugs that prolong the QT interval	Seizure - may increase risk 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

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Nortriptyline (Pamelor™)	Nortriptyline capsule 10mg 25mg 50mg 75mg	Depression Starting - 25mg a day Maintenance - 25 - 100mg a day given in 1 - 4 divided doses Max - 150mg a day Herpes zoster neuralgia (IDSA rec) Starting - 25mg at bedtime Max - 150mg a day Increase by 25 mg daily every 2–3 days as tolerated IDSA - Infectious disease society of America	Pamelor™ YES/$	May take without regard to food When taking doses > 100mg a day, plasma levels of nortriptyline should be monitored. Ideal plasma level is 50 - 150ng/ml.	Tricyclic antidepressant Inhibits norepinephrine and serotonin reuptake by neurons	Depression	Dry mouth - > 50% of patients in some trials Drowsiness- common Blurred vision Constipation Urinary retention Postural hypotension NOTE: Clomipramine is another TCA. It has the most extensive side effect information available. (see clomipramine above)	MAO inhibitors - DO NOT COMBINE Anticholinergic medications - may potentiate side effects Anticoagulant/Antiplatelet meds - may increase bleeding risk Serotonergic drugs - may increase risk of serotonin syndrome CYP2D6 inhibitors - may increase levels of nortriptyline Clonidine - nortriptyline may decrease the effectiveness of clonidine Valproic acid - valproic acid may increase nortriptyline levels Drugs that prolong the QT interval	Seizure - may increase risk 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

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• Serotonin modulators

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Trazodone (Desyrel®) (Oleptro™)	Trazodone tablet 50mg 100mg 150mg 300mg Oleptro® extended-release tablet 150mg 300mg	Depression Trazodone Starting - 150mg a day given in divided doses Maintenance - 150 - 400mg a day given in divided doses Max - 400mg a day Increase dose by 50mg/day every 3 - 4 days Oleptro™ Starting - 150mg once daily Maintenance - 150 - 300mg once daily Max - 375mg once daily Increase dose by 75mg/day every 3 days Sleep aid (off-label) Trazodone Starting - 50mg at bedtime Maintenance - 50 - 150mg at bedtime	Trazodone YES/$ Oleptro™ NO/$$$	Trazodone When taken after a meal or light snack, absorption is increased 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. Oleptro™ should be taken on an empty stomach, preferably at bedtime	Serotonin modulator Blocks postsynaptic serotonin receptors and inhibits postsynaptic serotonin reuptake	Depression Sleep aid - not FDA-approved	Drowsiness- 41%, P - 20% Dry mouth - 34%, P - 20% Dizzy/Lightheaded - 28%, P - 15% Headache- 20%, P - 16% Blurred vision - 15%, P - 4% Nausea - 13%, P - 10% Decreased libido - 1.3%, P - < 1% Orthostatic hypotension Priapism (erection lasting > 6 hours)	MAO inhibitors - DO NOT COMBINE Serotonergic drugs - may increase risk of serotonin syndrome Anticoagulant/Antiplatelet meds - may increase bleeding risk CYP3A4 inducers and inhibitors - may affect levels of trazodone Drugs that prolong the QT interval	Seizure - may increase risk 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

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Vilazodone (Viibryd®)	Viibryd® tablet 10mg 20mg 40mg Starter kit: 10mg X 7 20mg X 7 40mg X 16	Depression Starting - 10mg once daily for 7 days, then 20mg once daily for 7 days, then 40mg once daily Maintenance - 40mg once daily Max - 40mg once daily When taken with CYP3A4 strong inhibitors Dose should not exceed 20mg a day When taken with CYP3A4 moderate inhibitors Dose should not exceed 20mg a day in patients with significant side effects When taken with CYP3A4 strong inducers Consider doubling the dose Viibryd® dose should not exceed 80mg/day	Viibryd® NO/$$$$	Take with food. Food increases absorption.	Serotonin modulator Blocks postsynaptic serotonin receptors and inhibits postsynaptic serotonin reuptake	Depression	Diarrhea- 28%, P - 9% Nausea- 23%, P - 5% Dizziness- 9%, P - 5% Dry mouth - 8%, P - 5% Insomnia- 6%, P - 2% Decreased libido - 4%, P - < 1% Delayed ejaculation - 2%, P - 0%	MAO inhibitors - DO NOT COMBINE Serotonergic drugs - may increase risk of serotonin syndrome Anticoagulant/Antiplatelet meds - may increase bleeding risk CYP3A4 inducers and inhibitors - may affect levels of vilazodone	Seizure - may increase risk Glaucoma - may cause pupil dilation that precipitates angle-closure glaucoma Low sodium (hyponatremia) - may cause SIADH 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

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• Other

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Mirtazapine (Remeron®) (Remeron Soltab®)	Remeron® tablet 7.5mg 15mg 30mg 45mg Remeron Soltab® orally disintegrating tablet 15mg 30mg 45mg	Depression Starting - 15mg once daily at bedtime Maintenance - 15 - 45mg once daily at bedtime Max - 45mg once daily Increase dose at intervals of no less than 1 - 2 weeks	Remeron® YES/$	May take without regard to food 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.	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)	Depression	Somnolence- 54%, P - 18% Dry mouth - 25%, P - 15% Increased appetite - 17%, P - 2% Elevated cholesterol/triglycerides - 15%, P - 7% Constipation- 13%, P - 7% Weight gain - 12%, P - 2% Dizziness- 7%, P - 3% Elevated liver enzymes - 2%, P - 0.3% Sexual side effects are comparable to placebo in trials Orthostatic hypotension - may occur	MAO inhibitors - DO NOT COMBINE Mirtazapine is a CYP2D6, CYP1A2, and CYP3A substrate CYP2D6 inhibitors and inducers - may affect mirtazapine levels CYP1A2 inhibitors and inducers - may affect mirtazapine levels CYP3A4 inhibitors and inducers - may affect mirtazapine levels Serotonergic drugs - may increase risk of serotonin syndrome Phenytoin - may decrease mirtazapine levels by 45% Carbamazepine - may decrease mirtazapine levels by 60% Warfarin - mirtazapine may increase warfarin levels Cimetidine - may increase mirtazapine levels by more than 50% Ketoconazole - may increase mirtazapine levels by more than 50% Alpha blockers - mirtazapine may potentiate the effect of alpha blockers Anticholinergic medications - may potentiate side effects	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

Drug	Dosage form	Dosage	Generic/Price	Other	Class/Mechanism of Action	Indications (FDA-approved)	Side Effects P = % of patients on placebo who experienced side effect	Drug Interactions	Precautions/ Contraindications
Vortioxetine (Trintellix®) (formerly Brintellix®)	Trintellix® tablet 5mg 10mg 15mg 20mg	Depression Starting - 10mg once daily Maintenance - 20mg once daily Max - 20mg once daily When taken with CYP2D6 strong inhibitors Reduce dose by half CYP2D6 poor metabolizers Maximum dose is 10mg once daily When taken with CYP3A4 strong inducers Consider increasing the dose Dose should not exceed three times the original dose	Trintellix® NO/$$$$	May take without regard to food Brand name was changed in 2016 to avoid confusion with Brilinta	Serotonin Reuptake Inhibitor 5-HT3 receptor antagonist 5-HT1A receptor agonist	Depression	Nausea- 32%, P - 9% Dizziness- 9%, P - 6% Dry mouth -8%, P - 6% Constipation- 8%, P - 3% Sexual dysfunction - 5%, P - 2%	MAO inhibitors - DO NOT COMBINE Serotonergic drugs - may increase risk of serotonin syndrome Anticoagulant/Antiplatelet meds - may increase bleeding risk CYP2D6 strong inhibitors - reduce vortioxetine dose by half when coadministered CYP3A4 strong inducers - consider increasing vortioxetine dose when used together for > 14 days	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 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