1. Dosage

1.1. Adults

The FDA requires that all antidepressant drugs display a black box warning describing the potential for increased suicidal thinking and behavior compared to placebo when prescribed to young adults (18 to 24 years of age) with 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^1-2.

Citalopram is FDA approved for treatment of Major Depressive Disorder (MDD), Escitalopram is FDA approved for Generalized Anxiety Disorder (GAD) and MDD. Fluoxetine is FDA approved for Bipolar I Disorder (BD), Bulimia Nervosa (BN), Obsessive Compulsive Disorder (OCD), Panic Disorder (PD), Premenstrual Dysphoric Disorder (PMDD), and MDD. Fluvoxamine is FDA approved for OCD. Paroxetine is FDA approved for Seasonal Affective Disorder (SAD), Post Traumatic Stress Disorder (PTSD), Vasomotor Symptoms associated with Menopause (VMS), GAD, MDD, OCD, PDD, and PMDD. Sertraline is FDA approved for MDD, OCD, PD, SAD, PTSD, and PMDD. Olanzapine/Fluoxetine is FDA approved for Treatment Resistant Depression (TRD) and BD^1-17.

Maximum recommended daily doses for SSRI antidepressant drugs in adults, including the elderly population, are summarized in Tables 1 and 2 for both monotherapy and SSRI combination therapy, respectively. However, in all patients, the lowest effective antidepressant dose should be utilized to minimize unwanted adverse effects. Patient profiles with SSRI antidepressant dosages exceeding these recommendations will be reviewed.

Table 1: Oral SSRI Medications - Adult Maximum Recommended Dosages - Monotherapy^3-17
Drug Name	Available Dosage Strengths	Treatment Indication	Maximum Recommended Dosage
citalopram (Celexa®, generics)	10 mg, 20 mg, 40 mg tablets; 30 mg capsule; 10 mg/ 5 mL oral solution	MDD	Less than or equal to 65 years: 40 mg/day Greater than 65 years: 20 mg/day (older than 60 years)
escitalopram (Lexapro®, generics)	5 mg, 10 mg, 20 mg tablets; 5 mg/5 mL oral solution	GAD, MDD	Less than or equal to 65 years: 20 mg/day Greater than 65 years: 10 mg/day
fluoxetine (Prozac®, generics)	10 mg, 20 mg, 40 mg capsules; 10 mg, 20 mg, 40 mg, 60 mg tablets; 20 mg/5 mL solution	MDD, OCD	Less than or equal to 65 years: 80 mg/day Greater than 65 years: 80 mg/day
		BN, PD	Less than or equal to 65 years: 60 mg/day Greater than 65 years: 60 mg/day
		BD, TRD	Less than or equal to 65 years: 75 mg/day^ Greater than 65 years: 75 mg/day^
fluoxetine (Prozac® Weekly, generics)	90 mg delayed-release capsules	MDD	Less than or equal to 65 years: 90 mg/week Greater than 65 years: 90 mg/week
fluoxetine (Prozac Pulvules®)	10 mg, 20 mg, 40 mg pulvules	MDD, OCD	Less than or equal to 65 years: 80 mg/ day Greater than 65 years: 80 mg/ day
		BN, PD	Less than or equal to 65 years: 60 mg/ day Greater than 65 years: 60 mg/ day
		BD, TRD	Less than or equal to 65 years: 75 mg/day ^ Greater than 65 years: 75 mg/day ^
fluoxetine (generics)	10 mg, 20 mg capsules	PMDD	Less than or equal to 65 years: 80 mg/day Greater than 65 years: Not applicable
fluvoxamine (generics)	IR: 25 mg, 50 mg, 100 mg tablets ER: 100 mg, 150 mg 24-hour ER capsules	OCD	Less than or equal to 65 years: 300 mg/day* Greater than 65 years: 300 mg/day*
paroxetine mesylate (Pexeva®)	10 mg, 20 mg, 30 mg tablets	GAD, MDD	Less than or equal to 65 years: 50 mg/day++ Greater than 65 years: 40 mg/day
		OCD, PD	Less than or equal to 65 years: 60 mg/day Greater than 65 years: 40 mg/day
paroxetine HCl (Paxil®, generics)	10 mg, 20 mg, 30 mg, 40 mg tablets, 10 mg/ 5 mL suspension	OCD, PD	Less than or equal to 65 years: 60 mg/day++ Greater than 65 years: 40 mg/day
		MDD, PTSD	Less than or equal to 65 years: 50 mg/day Greater than 65 years: 40 mg/day
		SAD	Less than or equal to 65 years: 60 mg/day++ Greater than 65 years: 40 mg/day
		GAD	Less than or equal to 65 years: 50 mg/day++ Greater than 65 years: 40 mg/day
paroxetine HCl (Paxil CR®, generics)	12.5 mg, 25 mg, 37.5 mg 24-hour ER tablets	MDD	Less than or equal to 65 years: 62.5 mg/day Greater than 65 years: 50 mg/day
		PD	Less than or equal to 65 years: 75 mg/day Greater than 65 years: 50 mg/day
		SAD	Less than or equal to 65 years: 37.5 mg/day Greater than 65 years: 375 mg/day
		PMDD	Less than or equal to 65 years: 25 mg/day Greater than 65 years: Not applicable
Paroxetine mesylate (Brisdelle®, generics)	7.5 mg capsule	VMS	Less than or equal to 65 years: 7.5 mg/day at bedtime Greater than 65 years: 7.5 mg/day at bedtime
sertraline (Zoloft®, generics)	25 mg, 50 mg, 100 mg tablets; 20 mg/mL oral concentrate	MDD, OCD, PD, SAD, PTSD	Less than or equal to 65 years: 200 mg/day Greater than 65 years: 200 mg/day +
		PMDD	Less than or equal to 65 years: 150 mg/day Greater than 65 years: Not applicable

Legend:

BD = bipolar I disorder;
BN = bulimia nervosa
CR = controlled-release
ER = extended-release
GAD = generalized anxiety disorder
IR = immediate-release
MDD = major depressive disorder
OCD = obsessive-compulsive disorder
PD = panic disorder
PMDD = premenstrual dysphoric disorder
PTSD = posttraumatic stress disorder
SAD = social anxiety disorder
VMS = vasomotor symptoms associated with menopause
* Fluvoxamine IR doses greater than 100 mg daily should be administered in divided doses, if dose is unequal larger doses should be given at bedtime
++ Data do not confirm that paroxetine doses greater than 20 mg/day are more effective
+ Lower doses may be required in elderly patients
^ In combination with olanzapine

Table 2: Oral SSRI Medications - Adult Maximum Recommended Dosages – Combination Therapy^{1-2, 17}
Treatment Indication	Drug Name	Available Dosage Strengths	Maximum Recommended Dosage
BD, TRD	olanzapine/ fluoxetine (Symbyax®, generics)	3 mg/ 25 mg, 6 mg/ 25 mg, 12 mg/25 mg, 6 mg/ 50 mg, 12 mg/ 50 mg capsules	Less than or equal to 65 years 18 mg/ 75 mg per day Greater than 65 years: 18 mg/ 75 mg per day

Legend:

BD = bipolar I disorder
TRD = treatment-resistant depression

1.2. Pediatrics

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.

Citalopram and paroxetine are not FDA-approved for use in pediatric patients as safety and effectiveness in this age group have not been well established. The olanzapine/fluoxetine combination is FDA-approved in pediatric patients.

Maximum pediatric recommended doses for SSRI antidepressants approved for use as monotherapy and combination therapy are summarized in Tables 3 and 4, respectively. 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 3 and 4. Dosages exceeding these recommendations will be reviewed.

Table 3: Recommended SSRI Antidepressant Drug Dosages for Pediatric Patients – Monotherapy ^1-18
Drug Name	Available Dosage Strengths	Treatment Indication	Literature Based Maximum Dosage	FDA Approved Maximum Recommended Dosage
citalopram (Celexa®)	10 mg, 20 mg, 40 mg tablets; 30 mg capsule; 10 mg/ 5 mL oral solution		Greater than or equal to 6 years of age: 40 mg/ day	Not FDA approved for children & adolescents
escitalopram (Lexapro®, generics)	5 mg, 10 mg, 20 mg tablets; 5 mg/5 mL oral solution	MDD	6-11 years of age: 20 mg/ day Greater than or equal to 12 years of age: 30 mg/day	12 to 17 years of age: 20 mg/day
fluoxetine (Prozac®, generics)	10 mg, 20 mg, 40 mg capsules; 10 mg, 20 mg, 60 mg tablets; 20 mg/5 mL solution	MDD	Greater than or equal to 6 years of age: 60 mg/ day	8 to 17 years of age: 20 mg/day
		OCD	Greater than or equal to 6 years of age: 60 mg/ day	7 to 17 years of age: lower weight children: 30 mg/day higher weight children: 60 mg/day
fluoxetine (Prozac Pulvules®)	10 mg, 20 mg, 40 mg pulvules	BD		10 to 17 years of age: 50 mg/ day^
		MDD	8 to 18 years of age: 20 mg/day	8 to 18 years: 20 mg/day
		OCD	7 to 17 years of age: 60 mg/day	7 to 17 years: 60 mg/day
fluvoxamine (generics)	IR: 25 mg, 50 mg, 100 mg tablets	OCD	Age 8-11 years: 200 mg/day Age 12-17 years: 300 mg/day	8-11 years of age: 200 mg/day# 12 to 17 years of age: 300 mg/day#
Fluvoxamine controlled release (Luvox CR®, generics)	CR: 100 mg, 150 mg	OCD	Age 8-11 years: 200 mg/day Age 12-17 years: 300 mg/day	8-11 years of age: 200 mg/day 12 to 17 years of age: 300 mg/day
sertraline (Zoloft®, generics)	25 mg, 50 mg, 100 mg tablets; 20 mg/mL oral concentrate	OCD	Age greater than or equal to 6 years: 200 mg/day	6 to 17 years of age: 200 mg/day

Legend:

BD = bipolar I disorder
IR = immediate-release
MDD = major depressive disorder
OCD = obsessive-compulsive disorder
# Fluvoxamine IR doses > 50 mg daily should be administered in divided doses, if the two doses are unequal the larger dose should be given at bedtime
^ In combination with olanzapine

Table 4: Recommended SSRI Antidepressant Drug Dosages for Pediatric Patients – Combination Therapy^{1-2, 17-18}
Treatment Indication	Drug Name	Available Dosage Strengths	Literature Based Maximum Dosage	FDA Approved Maximum Recommended Dosage
BD	olanzapine/ fluoxetine (Symbyax®, generics)	3 mg/ 25 mg, 6 mg/ 25 mg, 12 mg/25 mg, 6 mg/ 50 mg, 12 mg/ 50 mg capsules	Age 10-17 years: 12 mg olanzapine/50 mg fluoxetine once daily	10 to 17 years of age: 12 mg/50 mg per day

Legend:

BD = bipolar I disorder

1.3. Renal Impairment

Many antidepressants do not require significant dosage modifications in renal impairment. However, dosage guidelines for select SSRIs in renal impairment are available. Table 5 summarizes dosage modifications and/or restrictions for specific SSRI antidepressant medications.

Table 5: Select SSRI Antidepressant Dosage Modifications in Renal Impairment^{1-5, 12-13}
Drug Name	Dosage in Renal Impairment
Citalopram	Severe renal impairment (creatinine clearance less than 20 mL/min): use cautiously, as specific dosage guidelines not available
Escitalopram	Severe renal impairment (creatinine clearance less than 20 mL/min): use cautiously, as specific dosage guidelines not available
Paroxetine (Paxil®, Pexeva®, Paxil CR®)	Serum levels, AUC increase as renal function declines; therefore, maximum doses when creatinine clearance less than 30 mL/min are: IR: 40 mg/day CR: 50 mg/day

Legend:

CR = controlled-release
IR = immediate-release