Which Antidepressant Should I Prescribe?

When it comes to antidepressants, there is no shortage of options. But how do psychiatrists choose antidepressants for their patients? This page is dedicated to reviewing a commonly used algorithm for choosing antidepressants in practice. Not all psychiatrists would agree with this approach, but we have found it very helpful in the consultation setting. Clinical trials used to bring medications to market typically exclude patients with complex medical or psychiatric histories. This makes choosing medications very difficult for these patients who are well known to be at higher risk for psychiatric conditions and who certainly benefit from psychotropic medications. 


Choosing an antidepressant often comes down to a combination of factors. These factors include the patient’s individual symptoms, the unique side effect profiles of each antidepressant, and the patient’s comorbid medical or psychiatric conditions. Antidepressant medications are generally safe but can be problematic in patients with complex medical conditions or who take many medications with potential drug interactions. Below we review a “Symptom-based” approach and a “Comorbidity-based” approach drawing on the currently available studies and theoretical mechanisms as discussed in the references below. 


It is important to note that the information provided here or anywhere on this website should never replace the medical advice of your physician. This information is primarily for prescribers of these medications. While this is a general guide, patients are individuals and this certainly does not apply to all patients. Thoughtful clinical judgment taking into account each patient’s complexity always carries more weight than any general approach or guide. With that, we hope you find this helpful and informative. 

Symptom-Based Choices:

Comorbidity-Based Choices:

Preferred Antidepressants in Liver Disease:


(NOTE: See Dosing Guidelines Below. Generally, start at half the typical starting dose and increase dose more slowly over time)



  1. Sertraline (Zoloft)
  2. Citalopram (Celexa)
  3. Escitalopram (Lexapro)


  1. Desvenlafaxine (Pristiq)


-Mirtazapine (Remeron)




  1. Duloxetine (Cymbalta)
  2. Venlafaxine (Effexor)
  3. Tricyclic Antidepressants
  4. Monoamine Oxidase Inhibitors


Adjust dose according to Child Pugh Score:


  1. Score A (5-6 points): 75-100% regular dose
  2. Score B (7-9 points): 50% regular dose
  3. Score C (10-15 points): CAUTION/AVOID USE


1 point

2 points

3 points

Albumin (g/dL)








Bilirubin (mg/dL)






Mild to Moderate (grade 1-2)

Severe (grade 3-4)

International Normalized Ratio





Medications Requiring Dose Adjustments in Liver Disease

SSRIsExtensively metabolized; decreased clearance and prolonged half-life. Initial dose should be reduced by 50%, with potentially longer dosing intervals between doses. Target doses are typically substantially lower than usual
MAOIsPotentially hepatotoxic. No dosing guidelines.
TCAs Extensively metabolized. Potentially serious hepatic effects. No dosing guidelines.
BupropionExtensively metabolized; decreased clearance. Reduce dose/frequency. In severe Cirrhosis, do not exceed 75mg/day for conventional tablets or 100mg/day for sustained release formulations
Desvenlafaxine Primarily metabolized by conjugation. No adjustment in starting dose needed in HI. Do not exceed 100mg/day in severe HI.
Venlafaxine Decreased clearance of venlafaxine and its active metabolite. Reduce dosage by 50% in mild to moderate HI, per manufacturer.
Duloxetine Extensively metabolized; reduced metabolism and elimination. Do not use in patients with any HI.
MirtazapineExtensively metabolized; decreased clearance. No dosing guidelines.
TrazodoneExtensively metabolized. No dosing guidelines.
ClozapineExtensively metabolized. Discontinue in patients with marked transaminase elevations or jaundice. No dosing guidelines.
Paliperidone Primarily renally excreted. No dosage adjustment needed.
Risperidone Extensively metabolized. Free fraction increased 35%. Starting dosage and dose increments not to exceed 0.5mg twice daily. Increases >1.5mg twice daily should be made at intervals of > 1 week.
Quetiapine Extensively metabolized. Clearance decreased 30%. Start at 25mg/day and increase by 25-50mg/day.
Ziprasidone Extensively metabolized; increased half-life and serum level in mild to moderate HI. In spite of this, manufacturer recommends no dosage adjustment.
TypicalsAll metabolized in liver. No specific dosing recommendations. Avoid phenothiazines (thioridazine, trifluoperazine, thorazine) due to cholestatic hepatotoxicity. Reduce starting dose of all typicals and titrate slowly.
Alprazolam Decreased metabolism and increased half-life. Reduce dosage by 50%. Avoid use in patients with cirrhosis.
Chlordiazepoxide, clonazepam, diazepamExtensively metabolized. Reduced clearance and prolonged half-life. Avoid use if possible.
BuspironeExtensively metabolized. Half-life may be prolonged. Reduce dosage and frequency in mild to moderate cirrhosis. Do not use in patients with severe HI.
Valproate Extensively metabolized; reduced clearance and increased half-life. Reduce dosage; monitor liver function tests frequently, especially in first 6 months of therapy. Avoid in severe HI if possible.
Lamotrigine Initial, escalation, and maintenance dosages should be reduced by 50% in moderate HI (Child-Pugh B) and by 75% in severe HI (Child-Pugh C).



Antidepressants with hepatotoxic potential:


  1. Duloxetine
  2. Monoamine Oxidase Inhibitors (MAOIs)
  3. Nefazodone


Elevated Transaminases (ALT>AST) seen mostly with:


  1. TCAs
  2. SNRIs

Antidepressants in Cardiovascular Disease


Most Evidence for Safety:

  1. Sertraline (Zoloft) – SAD HEART trial (efficacy limited to recurrent depression, depression before cardiac event, or severe depression with HAM-D >20; trend toward reduced adverse cardiac events); ENRICHED trial (reduced mortality, reduced adverse cardiac events)
  2. Mirtazapine (Remeron) – MIND-IT Trials
  3. Citalopram (Celexa) – CREATE trial
  4. Escitalopram (Lexapro) – EsDEPACS trial (Kim et al. 2015)
  5. Nortriptyline (50-150ng/mL): relatively well tolerated in patients with impaired left ventricular dysfunction (Roose and Glassman 1989); TCAs have Type 1A (quinidine like) properties; TCA Users had increased risk of incident MI (Cohen 2000)
  6. Paroxetine: Limited data suggesting preferential role in congestive heart failure
  7. Coronary Artery Disease: Escitalopram, Citalopram, and Sertraline are first line
  8. Heart Failure: Consider Paroxetine, Mirtazapine, Bupropion, Venlafaxine, or Duloxetine (monitor blood pressure)
  9. TCAs, Trazodone, and Mirtazapine (antihistamine properties) may increase appetite, promote weight gain, and help insomnia in patients with cardiac cachexia
  10. Bupropion for weight loss or smoking cessation
  11. Anti-platelet effect of SSRIs in ischemic Heart disease may be helpful but unknown if clinically significant


Increased QTc prolongation Risk

  1. Citalopram (Celexa) >40mg / day
  2. Escitalopram (Lexapro) >20mg / day
  3. Tricyclic Antidepressants
  4. Venlafaxine (Effexor)
  5. Mirtazapine (Remeron)


Risk Factors for Torsades de pointes:

  1. Hypokalemia
  2. History of prolonged QT
  3. High doses
  4. Multiple QT prolonging agents
  5. Any history of cardiac disease
  6. Female gender

Antidepressants in Renal Disease


All antidepressants may be used in patients with renal failure


-As a general rule, start low and go slow

-Caution with renally excreted antidepressants in ESRD (paroxetine, desvenlafaxine, venlafaxine*)

-Patients with ESRD more sensitive to side effects of TCAs (if used, nortriptyline and desipramine are preferred)

*Note that Venlafaxine half-life is prolonged in renal insufficiency and its clearance is reduced by more than 50% in patients undergoing dialysis

**Note that a large retrospective study found no increased adverse effects of higher versus lower doses of paroxetine, mirtazapine, and venlafaxine


Pharmacokinetics/Pharmacodynamics in Renal Disease

  1. Caution with renally excreted drugs in ESRD (lithium, gabapentin, pregabalin, topiramate, paliperidone, risperidone, paroxetine, desvenlafaxine, venlafaxine, memantine)
  2. Edema is often present in ESRD, increasing volume of distribution for hydrophilic drugs
  3. Uremic products circulating in ESRD may displace protein bound drugs! Always try to get free drug levels when monitoring as total drug levels can be misleading
  4. Chronic renal disease can significantly modify phase 1 and 2 hepatic metabolism (reduction in P450 2C9, 2C19, 2D6, 3A4 metabolism).
  5. Do not overlook potential impairment in renal metabolism as well (drugs are metabolized in the kidney as well as liver).
  6. In general, in patients with renal insufficiency, use the rule of “two-thirds” (2/3 the normal dose)
  7. Electrolyte disturbances in renal failure or diuretic therapy may increase the risk of cardiac arrhythmias especially in pts receiving QT prolonging agents


Antidepressants and effects on Genitourinary (GU) system:


Effect on Kidneys

SSRIs/SNRIsSIADH, Polydipsia, Hyponatremia,

TCAs & Anticholinergics

Urinary retention, Urinary hesitancy, SIADH, hyponatremia, psychogenic polydipsia  

Duloxetine Urinary retention



Hemodialysis (HD) Patients:

  1. Up to 70% of patient older than 55 have moderate to severe chronic cog impairment
  2. Duloxetine is not properly excreted in HD (CNS Toxic)
  3. Mirtazapine and Amitriptyline levels ↓ after HD
  4. Fluoxetine (and norfluoxetine) levels not affected
  5. TCAs have longer elimination half-life in HD pts
  6. Be careful with medications prone to cause orthostasis as HD patients have rapid fluid shifts and are very susceptible to orthostatic hypotension

Antidepressants in Rheumatology Disorders


Rheumatoid Arthritis:

  1. Sertraline (little side effects up to 100mg/day)
  2. Doxepin (some data)
  3. Paroxetine (20-40mg/d) and Amitriptyline (75mg-150mg/d): Similar efficacy for pain/depression but paroxetine better tolerated
  4. SNRIs (Duloxetine, Venlafaxine)



  1. Duloxetine for elderly patients with osteoarthritis
  2. Venlafaxine (Effexor)
  3. Desvenlafaxine (Pristiq)


Chronic Pain

  1. Nortriptyline (low doses)
  2. Amitriptyline (low doses)
  3. SNRIs 




Psychiatric Side Effects of Medications used in treating Rheumatology Disorders



Psychiatric Side Effects




Mood lability, euphoria, irritability, anxiety, insomnia, mania, depression, psychosis, delirium, cognitive disturbance


Delirium (at high doses)


Anxiety, delirium, visual hallucinations


Confusion, psychosis, mania, depression, nightmares, anxiety, aggression, delirium

Immunoglobulin (IV)

Delirium, agitation




Delirium (at high doses)

Mycophenolate mofetil

Anxiety, depression, sedation (all rare)

NSAIDs (high dose)

Depression, anxiety, paranoia, hallucinations, concentration, hostility, confusion, delirium


Insomnia, depression, hallucinations


Anxiety, delirium, insomnia, restlessness

Evidence for efficacy and safety of Antidepressants in individuals with Respiratory Diseases exists for:

  1. Citalopram
  2. Sertraline
  3. Paroxetine
  4. Nortriptyline
  5. Desipramine
  6. Buspirone (Buspar)
  7. Modafanil
  8. Atomoxetine
  9. Zolpidem
  10. Zopiclone
  11. Melatonin
  12. Ramelteon



Try to avoid the following medications in patients with respiratory diseases:


  1. Obstructive Sleep Apnea (OSA): Mirtazapine, TCAs, Benzodiazepines
  2. Asthma/COPD: Highly anticholinergic antipsychotics, beta blockers


Carbamazepine has elevated risk of diffuse parenchymal lung disease

Antidepressants in Patients with Neurological Disease



  1. SSRIs (Citalopram, Sertraline, Fluoxetine)
  2. Stimulants (dextroamphetamines, Ritalin)
  3. Nortriptyline


Pseudobulbar Affect:

  1. Citalopram, Sertraline
  2. Nuedexta


Parkinson’s Disease (PD):


PD Depression:

  1. Pramipexole
  2. SSRIs
  3. TCAs
  4. Duloxetine
  5. Pimavanserin (case studies)


Traumatic Brain Injury:


Depression secondary to TBI

  1. SSRIs (start low and go slow)


Post-Concussion Headache:

  1. Amitriptyline  


Mania and Labile Mood:

  1. Valproic acid
  2. Carbamazepine


Cognitive Enhancement:

  1. Stimulants  (methylphenidate > amphetamines) 
  2. Milnacipran
  3. SSRIs (Controversial results)
  4. Acetylcholinesterase inhibitors



Antidepressants During Pregnancy:




  1. SSRIs
  2. Sertraline
  3. Fluoxetine
  4. Citalopram
  5. Escitalopram


SAFE (but less data)


  1. Bupropion (Wellbutrin)
  2. Venlafaxine (Effexor)
  3. Duloxetine (Cymbalta)


AVOID (if possible)

  1. Paroxetine
  2. TCAs
  3. MAOIs
  4. Mirtazapine


Antidepressants in Breastfeeding:





  1. Sertraline
  2. Fluoxetine
  3. Citalopram
  4. Paroxetine

For more information or to review more topics in psychopharmacology, visit the psychopharmacology station!



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  7. Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.
  8. Stern, T. A., Freudenreich, O., Fricchione, G., Rosenbaum, J. F., & Smith, F. A. (2018). Massachusetts General Hospital handbook of general hospital psychiatry. Edinburgh: Elsevier.
  9. McCarron, Robert M., et al. Lippincotts Primary Care Psychiatry: for Primary Care Clinicians and Trainees, Medical Specialists, Neurologists, Emergency Medical Professionals, Mental Health Providers, and Trainees. Wolters Kluwer Health/Lippincott Williams & Wilkins, 2009.
  10. Levenson, J. L. (2019). The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. Washington, D.C.: American Psychiatric Association Publishing.
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