The FDA requires that all antidepressant drugs display a black box warning describing the potential for increased suicidal thinking and behavior when prescribed to young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders. In short-term clinical trials, the suicide risk was increased in young adults managed with antidepressants compared to those receiving placebo in the first few months of treatment. Suicide risk was not shown to increase in adults over 24 years of age, and patients 65 years of age and older manifested a decreased suicide risk. Patients of all ages prescribed antidepressant drugs should be closely monitored for changes in behavior, clinical worsening, or suicidality. When treating elderly patients, caution is indicated when administering these medications due to risk of hyponatremia ^1-43.

Nonselective serotonin reuptake inhibitor monotherapy antidepressant drugs are FDA-approved for use in MDD, obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD). Additionally, bupropion is FDA-approved for seasonal affective disorder (AD) and smoking cessation (SC), milnacipran is FDA-approved for fibromyalgia (F) management, and duloxetine is FDA-approved for neuropathic pain (NP), F, and chronic musculoskeletal pain in adults (CMP). Recently, doxepin has received FDA approval for insomnia in adults (I). Vilazodone, a selective serotonin reuptake inhibitor (SSRI) as well as a partial agonist at the 5-HT1A receptor, is FDA-approved for MDD. Levomilnacipran (Fetzima®), a serotonin and norepinephrine reuptake inhibitor (SNRI) and an enantiomer of milnacipran, has also been FDA-approved for use in treating MDD. The antidepressant agent, vortioxetine, an SSRI that also acts as an agonist at 5-HT1A receptors and an antagonist at 5-HT3 receptors, has gained FDA approval to manage MDD. Combination therapy is FDA-approved for severe depression, and moderate anxiety/agitation/depression ^1-43.

Maximum recommended daily doses for antidepressant drugs in adults, including the elderly population, are summarized in Tables 1-6. Maximum recommended dosages for antidepressant combination therapy are summarized in Table 7. However, in all patients, the lowest effective antidepressant dose should be utilized to minimize unwanted adverse effects. Patient profiles with antidepressant dosages exceeding these recommendations will be reviewed.

Table 1: Adult and Elderly Maximum Recommended Antidepressant Dosages (Monotherapy) - Tricyclic Antidepressants^1-18

Drug Name	Available Dosage Strengths	Treatment Indication	Maximum Recommended Dosage
amitriptyline	generics: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg tablets	MDD	Less than or equal to 65 years: 150 mg/day Greater than 65 years: 150 mg/day divided into three doses
amoxapine (generics)	25 mg, 50 mg, 100 mg, 150 mg tablets	MDD	Less than or equal to 65 years: 400 mg/day* Greater than 65 years: 300 mg/day *
clomipramine (Anafranil®, generics)	25 mg, 50 mg 75 mg capsules	OCD	Less than or equal to 65 years: 250 mg/day Greater than 65 years: 250 mg/day
desipramine (generics)	10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg tablets	MDD	Less than or equal to 65 years: 300 mg/day Greater than 65 years: 150 mg/day
doxepin (generics)	10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg capsules; 10 mg/mL oral concentrate	MDD	Less than or equal to 65 years: mild to moderate illness: 150 mg/day Greater than 65 years: mild to moderate illness: 150 mg/day
			Less than or equal to 65 years: severe illness: 300 mg/day Greater than 65 years: severe illness: 300 mg/day
			Less than or equal to 65 years: mild to moderate illness: 150 mg/day Greater than 65 years: mild to moderate illness: 150 mg/day
			Less than or equal to 65 years: severe illness: 300 mg/day Greater than 65 years: severe illness: 300 mg/day
doxepin (Silenor®)	3 mg, 6 mg tablets	I	Less than or equal to 65 years: 6 mg/day Greater than 65 years: 6 mg/day
imipramine (Tofranil®, generics)	generics:10 mg, 25 mg, 50 mg tablets; 75 mg 100 mg, 125 mg, 150 mg capsules Tofranil®: 10 mg, 25 mg tablets	MDD	Less than or equal to 65 years: 200 mg/day Greater than 65 years: 100 mg/day ^
imipramine pamoate (generics)	generics: 10 mg, 25 mg, 50 mg tablets; Tofranil®: 10 mg, 25 mg tablets
nortriptyline (Pamelor®, generics)	10 mg, 25 mg, 50 mg, 75 mg capsules; 10 mg/5 mL oral solution (generic only)	MDD	Less than or equal to 65 years: 150 mg/day Greater than 65 years: 50 mg/day
protriptyline (generics)	5 mg, 10 mg tablets	MDD	Less than or equal to 65 years: 60 mg/day Greater than 65 years: 20 mg/day+
trimipramine (generics)	25 mg, 50 mg 100 mg capsules	MDD	Less than or equal to 65 years: 200 mg/day Greater than 65 years: 100 mg/day

Legend:

• I = insomnia
• MDD = major depressive disorder
• OCD = obsessive-compulsive disorder 
• * The maximum amoxapine dose in elderly patients and in most adults is 300 mg/day. Those patients Less than or equal to 65 years of age who have not responded adequately to a two-week trial utilizing 300 mg/day may receive a trial of 400 mg amoxapine per day.  
• #Doxepin is also recommended for depression and anxiety associated with psychoneurosis, alcoholism, and organic disease.
• ^ May increase to 150 mg/day, if needed; doses over 200 mg are not recommended; doses usually do not exceed 100 mg/day in geriatric patients.
• ** When doses above 100 mg daily are administered, plasma levels of nortriptyline should be maintained in the optimum range of 50 ng/mL to 150 ng/mL.
• + Elderly patients should usually be given lower than average protriptyline doses. Elderly patients receiving protriptyline doses greater than 20 mg daily should receive close cardiac monitoring.

Table 2: Adult and Elderly Maximum Recommended Antidepressant Dosages (Monotherapy) - Tetracyclic Antidepressants^{1-2, 19-20}

Drug Name	Available Dosage Strengths	Treatment Indication	Maximum Recommended Dosage
mirtazapine (Remeron®, generics)	7.5 mg, 15 mg, 30 mg, 45 mg tablets; 15 mg, 30 mg, 45 mg orally disintegrating tablets	MDD	Less than or equal to 65 years: 45 mg/day Greater than 65 years: 45 mg/day

Legend:

• MDD = major depressive disorder 

Table 3: Adult and Elderly Maximum Recommended Antidepressant Dosages (Monotherapy) - Monoamine Oxidase Inhibitors ^{1-2, 21-25}

Drug Name	Available Dosage Strengths	Treatment Indication	Maximum Recommended Dosage
isocarboxazid (Marplan®)	10 mg tablets	MDD	Less than or equal to 65 years: 60 mg/day Greater than 65 years: 60 mg/day *
phenelzine (Nardil®, generics)	15 mg tablets	Depression*	Less than or equal to 65 years: 90 mg/day Greater than 65 years: 90 mg/day *
selegiline (EMSAM®) transdermal patch	6 mg/ 24 hours, 9 mg/ 24 hours, 12 mg/ 24 hours transdermal patch	MDD	Less than or equal to 65 years: 12 mg/ 24 hours Greater than 65 years: 6 mg/24 hours
tranylcypromine (Parnate®, generics)	10 mg tablets	MDD	Less than or equal to 65 years: 60 mg/day Greater than 65 years: 60 mg/day*

Legend:

• MDD = major depressive disorder
• ▪ Use MAOIs cautiously in elderly patients due to a greater risk of morbidity if hypertensive crisis develops.
• * Phenelzine has been found to be effective in depressed patients clinically characterized as "atypical,” “nonendogenous,” or “neurotic.”
• ^ Indicated for MDD in patients who have not responded adequately to other antidepressants.

Table 4: Adult and Elderly Maximum Recommended Antidepressant Dosages (Monotherapy) – Serotonin and Norepinephrine Reuptake Inhibitors ^{1-2, 26-32}

Drug Name	Available Dosage Strengths	Treatment Indication	Maximum Recommended Dosage
desvenlafaxine (Pristiq®, generics)	25 mg, 50 mg 100 mg 24-hour ER tablets	MDD	Less than or equal to 65 years: 400 mg/day^ Greater than 65 years: 400 mg/day^
duloxetine (Cymbalta®, Drizalma Sprinkle®, generics)	30 mg, 60 mg delayed-release capsules Generic only: 20, 40 mg	CMP, F, NP	Less than or equal to 65 years: 60 mg/day Greater than 65 years: 60 mg/day
		GAD, MDD	Less than or equal to 65 years: 120 mg/day # Greater than 65 years:     120 mg/day #
levomilnacipran (Fetzima®)	20 mg, 40 mg 80 mg, 120 mg 24-hour ER capsules	MDD	Less than or equal to 65 years: 120 mg/day Greater than 65 years: 120 mg/day
milnacipran (Savella®)12.5 mg, 25 mg, 50 mg 100 mg tablets	12.5 mg, 25 mg, 50 mg 100 mg tablets	F	Less than or equal to 65 years: 200 mg/day Greater than 65 years: 200 mg/day
venlafaxine (generics)	25 mg, 37.5 mg, 50 mg, 75 mg, 100 mg IR tablets	MDD	Less than or equal to 65 years: 375 mg/day ~ Greater than 65 years: 375 mg/day ~
venlafaxine (Effexor XR®, generics)	37.5 mg, 75 mg, 150 mg 24-hour ER capsules		Less than or equal to 65 years: 225 mg/day Greater than 65 years: 225 mg/day
		SAD	Less than or equal to 65 years: 75 mg/day Greater than 65 years: 75 mg/day
venlafaxine (generics)	37.5 mg, 75 mg, 150 mg, 225 mg 24-hour ER tablets	MDD	Less than or equal to 65 years: 225 mg/day Greater than 65 years: 225 mg/day
		SAD	Less than or equal to 65 years: 75 mg/day Greater than 65 years: 75 mg/day

Legend:

• CMP = chronic musculoskeletal pain
• F = fibromyalgia
• GAD = generalized anxiety disorder
• MDD = major depressive disorder
• NP = neuropathic pain
• PD = panic disorder
• SAD = social anxiety disorder
• ^ In studies, desvenlafaxine doses up to 400 mg per day were no more effective than 50 mg daily doses and were associated with increased adverse events.
• # Duloxetine doses of 120 mg, while effective, are no more effective than 60 mg daily doses.
• ~ The maximum recommended venlafaxine dose is 225 mg/day for moderately depressed outpatients. Dosages Greater than 225 mg/day in moderately depressed outpatients do not demonstrate additional efficacy. However, more severely depressed inpatients may respond to venlafaxine dosages up to 375 mg/day.

Table 5: Adult and Elderly Maximum Recommended Antidepressant Dosages (Monotherapy) – Selective Serotonin Reuptake Inhibitors (SSRIs)/5-HT1A Receptor Agonists and SSRIs/5-HT1A Receptor Agonists/5-HT3 Receptor Antagonists ^{1-2, 33-34}

Drug Name	Available Dosage Strengths	Treatment Indication	Maximum Recommended Dosage
vilazodone (Viibryd®)	10 mg, 20 mg, 40 mg tablets	MDD	Less than or equal to 65 years: 40 mg/day Greater than  65 years: 40 mg/day
vortioxetine (Trintellix®)	5 mg, 10 mg, 20 mg tablets	MDD	Less than or equal to 65 years: 20 mg/day Greater than  65 years:     20 mg/day

Legend:

• MDD = major depressive disorder 

-----

Table 6: Adult and Elderly Maximum Recommended Antidepressant Dosages (Monotherapy) – Miscellaneous Agents^{1-2, 35-40}

Drug Name	Available Dosage Strengths	Treatment Indication	Maximum Recommended Dosage
bupropion (generics)	75 mg, 100 mg IR tablets	MDD	Less than or equal to 65 years: 450 mg/day Greater than 65 years: 450 mg/day
bupropion (Forfivo XL®, Wellbutrin XL®, generics)	Wellbutrin XL®, generics: 150 mg, 300 mg 24-hour ER tablets Forfivo XL®, generics: 450 mg 24-hour-ER tablets	MDD	Less than or equal to 65 years: 450 mg/day Greater than 65 years: 450 mg/day
bupropion (Wellbutrin SR®, generics)	100 mg, 150 mg, 200 mg 12-hour ER tablets	MDD	Less than or equal to 65 years: 400 mg/day Greater than 65 years: 400 mg/day
bupropion (Aplenzin®)	174 mg, 348 mg, 522 mg 24-hour ER tablets	MDD	Less than or equal to 65 years: 522 mg/day Greater than 65 years: 522 mg/day
		AD	Less than or equal to 65 years: 348 mg/day Greater than 65 years: 348 mg/day
bupropion (Wellbutrin XL®, generics)	Wellbutrin XL®, generics: 150 mg, 300 mg 24-hour ER tablets	AD	Less than or equal to 65 years: 300 mg/day Greater than 65 years: 300 mg/day
bupropion (generics)	150 mg 12-hour ER tablets	SC	Less than or equal to 65 years: 300 mg/day Greater than 65 years: 300 mg/day
nefazodone (generics)	50 mg, 100 mg, 150 mg, 200 mg, 250 mg tablets	MDD	Less than or equal to 65 years: 600 mg/day Greater than 65 years: 600 mg/day
trazodone (generics)	50 mg, 100 mg, 150 mg, 300 mg IR tablets	MDD	Less than or equal to 65 years: outpatients: 400 mg/day Greater than 65 years: outpatients: 400 mg/day

Legend:

• AD = seasonal affective disorder
• MDD = major depressive disorder
• SC = smoking cessation

Table 7: Adult Maximum Recommended Antidepressant Dosages (Combination Therapy) ^{1-2, 41-42}

Treatment Indication	Drug Name	Available Dosage Strengths	Maximum Recommended Dosage
severe depression	chlordiazepoxide/ amitriptyline (generics)	5 mg/ 12.5 mg, 10 mg/25 mg tablets	60 mg/150 mg/day *
anxiety/agitation/depression	perphenazine/ amitriptyline (generics)	2 mg/10 mg, 4 mg/10 mg, 2 mg/25 mg, 4 mg/25 mg, 4 mg/50 mg tablets	16 mg/200 mg/day

Legend:

• * Lower chlordiazepoxide/amitriptyline dosages and close monitoring are recommended in elderly patients due to greater risks for impaired cognitive/motor function.

The FDA requires that all antidepressant drugs display a black box warning describing the potential for increased suicidal thinking and behavior when prescribed to children and adolescents with MDD and other psychiatric disorders. In short-term clinical trials, the suicide risk occurred twice as frequently with antidepressant-treated children/adolescents compared to those receiving placebo (4% vs. 2%, respectively) in the first few months of treatment. Pediatric patients prescribed antidepressant drugs should be closely monitored for changes in behavior.

Maximum recommended doses for non-SSRI antidepressants approved for use as monotherapy in pediatric patients are summarized in Tables 8-10. An additional column reflecting literature-based dosing included in the Texas Health and Human Services Psychotropic Medication Utilization Parameters for Children and Youth in Texas Public Behavioral Health (6th Version) is included in Tables 8-11. Dosages exceeding these recommendations will be reviewed.

Table 8: Pediatric Maximum Recommended Antidepressant Drug Dosages (Monotherapy) - Tricyclic Antidepressants^{1-2, 3-4, 6-9, 12-18, 44}

Drug Name	Available Dosage Strengths	Treatment Indication	Literature Based Maximum Dosage	FDA Approved Maximum Recommended Dosage
amitriptyline (generics)	generics: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg tablets	MDD	Reviewed but not included/ recommended	Greater than 12 years of age: 50 mg daily divided into three doses^
clomipramine (Anafranil®, generics)	25 mg, 50 mg 75 mg capsules	OCD	Age 10-17 years: 3 mg/kg/day or 200 mg/ day, whichever is less	Greater than or equal to 10 years of age: 3 mg/kg/day or 200 mg/day, whichever is less
desipramine (Norpramin®, generics)	generics: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg tablets Norpramin®: 10 mg, 25 mg tablets	aa	Reviewed but not included/ recommended	adolescents:   150 mg/day
imipramine (Tofranil®, generics)	generics:10 mg, 25 mg, 50 mg tablets; Tofranil®: 10 mg, 25 mg, 50 mg tablets	MDD	Reviewed but not included/ recommended	adolescents: 100 mg/day
		nocturnal enuresis		6-11 years of age: 2.5 mg/kg/day up to 50 mg/day Greater than or equal to 12 years of age: 2.5 mg/kg/day up to 75 mg/day
nortriptyline (Pamelor®, generics)	10 mg, 25 mg, 50 mg, 75 mg capsules; 10 mg/5 mL oral solution (generic only)	MDD	Reviewed but not included/ recommended	adolescents: 50 mg/day
protriptyline	5 mg, 10 mg tablets	MDD	Reviewed but not included/ recommended	adolescents:   30 mg/day*
trimipramine (generics)	25 mg, 50 mg 100 mg capsules	MDD	Reviewed but not included/recommended	adolescents:   100 mg/day

Legend:

• MDD = major depressive disorder
• OCD = obsessive-compulsive disorder
• ^ In general, lower dosages are recommended for these patients. Ten milligrams 3 times daily with 20 mg at bedtime may be satisfactory in adolescent and elderly patients who do not tolerate higher dosages.
• # imipramine pamoate is not approved for pediatric use
• * Adolescents should usually be given lower than average protriptyline doses

Table 9: Pediatric Maximum Recommended Antidepressant Drug Dosages (Monotherapy)– Monoamine Oxidase Inhibitors^{1-2, 21, 24, 44}

Drug Name	Available Dosage Strengths	Treatment Indication	Literature Based Maximum Dosage	FDA Approved Maximum Recommended Dosage
isocarboxazid (Marplan®)	10 mg tablets	MDD	Not reviewed	Greater than or equal to 16 years of age:   60 mg/day
selegiline (EMSAM®) transdermal patch	6 mg/ 24 hours, 9 mg/ 24 hours, 12 mg/ 24 hours transdermal patch	MDD	Age ≥ 12 years: 12 mg per 24 hours	Not approved for pediatric use

Legend:

• MDD = major depressive disorder

Table 10: Pediatric Maximum Recommended Antidepressant Drug Dosages (Monotherapy) – Serotonin and Norepinephrine Reuptake Inhibitors^{1-2, 26-28, 44}

	Drug Name	Available Dosage Strengths	Treatment Indication	Literature Based Maximum Dosage	FDA Approved Maximum Recommended Dosage
	desvenlafaxine (Pristiq®, generics)	25 mg, 50 mg 100 mg 24-hour ER tablets	Major depressive disorder	Age 7-17 years: 50 mg/day	Not approved for pediatric use
	duloxetine (Cymbalta®, generics)	20 mg, 30 mg, 40 mg 60 mg delayed-release capsules	General anxiety disorder	Age 7-17 years: 120 mg/day	7-17 years of age:   120 mg/day
			Fibromyalgia		13 years of age: 60 mg/ day

Table 11: Pediatric Maximum Recommended Antidepressant Drug Dosages (Monotherapy) - Tetracyclic Antidepressants ^{1-2, 19-20, 44}

Drug Name	Available Dosage Strengths	Treatment Indication	Literature Based Maximum Dosage	FDA Approved Maximum Recommended Dosage
mirtazapine (Remeron®, generics)	7.5 mg, 15 mg, 30 mg, 45 mg tablets; 15 mg, 30 mg, 45 mg orally disintegrating tablets	Major depressive disorder	Age greater than or equal to 3 years: 45 mg/day	Not approved for pediatric use

Many antidepressants do not require significant dosage modifications in renal impairment. However, dosage guidelines for select non-SSRI antidepressants in renal impairment are available. Tables 12-15 summarizes dosage modifications and/or restrictions for specific non-SSRI antidepressant medications.

Table 12: Select non-SSRI Antidepressant Dosage Modifications in Renal Impairment – Tetracyclic Antidepressants^{1-2, 19-20}

Drug Name	Dosage in Renal Impairment
Mirtazapine	Initiate with the lowest dosage and titrate slowly as renal clearance reduced by approximately 30% in moderate (Creatinine clearance 11-39 ml/min) and 50% in severe (Creatinine clearance less than 10 ml/min) renal impairment

Table 13: Select non-SSRI Antidepressant Dosage Modifications in Renal Impairment – Monoamine Oxidase Inhibitors^{1-2, 21-23, 25}

Drug Name	Dosage in Renal Impairment
Isocarboxazid	Contraindicated in severe renal impairment; use cautiously in moderate renal impairment due to potential accumulation of active metabolites
Phenelzine	Contraindicated for use in severe renal impairment

Table 14: Select non-SSRI Antidepressant Dosage Modifications in Renal Impairment – Serotonin and Norepinephrine Reuptake Inhibitors ^{1-2, 26-32}

Drug Name	Dosage in Renal Impairment
Desvenlafaxine	Moderate renal impairment (CrCl 30-50 ml/min): 50 mg/day Severe renal impairment (CrCl less than 30 ml/min), ESRD: 25 mg once daily or 50 mg every other day
Duloxetine	Mild to moderate renal impairment: start with lower dose, titrate gradually Severe renal impairment (GFR less than 30 ml/min) ESRD: avoid use
Levomilnacipran	Moderate renal impairment (CrCl 30-59 ml/min): 80 mg/day Severe renal impairment (CrCl 15-29 ml/min): 40 mg/day ESRD: not recommended
Milnacipran	Moderate renal impairment (CrCl 30-49 ml/min): use cautiously Severe renal impairment (CrCl 5-29 ml/min): reduce dose by 50% to 25 mg twice daily or -50 mg once daily (based on response and tolerability) ESRD: not recommended
Venlafaxine	Mild to moderate renal impairment (CrCl 30-89 ml/min): IR:  reduce total daily dose by 25% ER:  reduce total daily dose by 25% to 50% Severe renal impairment (CrCl less than 30 ml/min) and hemodialysis: reduce total daily dose by 50% Adjust doses based on response and tolerability due to variability in renal clearance

Legend:

• CrCl = creatinine clearance
• ESRD = end-stage renal disease
• ER = extended-release
• IR = immediate-release 

Table 15: Select non-SSRI Antidepressant Dosage Modifications in Renal Impairment – Other Miscellaneous Agents^{1-2, 35-38, 40}

Drug Name	Dosage in Renal Impairment
Bupropion	Administer cautiously in renal impairment due to potential for accumulation and risk for adverse events (e.g., seizures); consider reduced dosage/dosage frequency Forfivo™ XL: not recommended in renal impairment as no lower dose available
Trazodone	Use cautiously in patients with renal impairment

Legend:

• CrCl = creatinine clearance