1.1. Adults

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 Antidepressants1-18
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 Antidepressants1-2, 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 

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Table 6: Adult and Elderly Maximum Recommended Antidepressant Dosages (Monotherapy) – Miscellaneous Agents1-2, 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.