Have you found it hard to stay on traditional psychiatric medications? If so, many clients like yourself find it challenging to adhere to psychiatric treatment regimens due to the difficult and sometimes intolerable side effect spectrum. You are not alone! In an effort to shed light on this topic, in today’s post Dr. Pullara reviews the side effect profiles of the top 5 most widely prescribed medications used to treat depression, PTSD, and anxiety: Lexapro, Cymbalta, Prozac, Zoloft, Effexor, and Wellbutrin. Furthermore, he reviews the side effect profile of Ketamine to see how it compares.

Note: Sources for the following numbers come from www.uptodate.com. This website is a trusted online medical resource that provides up-to-date, evidence-based information about a wide range of conditions and treatments, helping medical professionals stay up-to-date and provide the best possible care. It features comprehensive articles and reviews written by experts in the field, giving practitioners access to accurate and authoritative information to inform and improve medical decision-making. 

Table of Contents

  1. Lexapro

  2. Cymbalta

  3. Prozac

  4. Zoloft

  5. Effexor

  6. Wellbutrin

  7. Low-dose IV Ketamine

1. Lexapro (escitalopram)

Lexapro is a selective serotonin reuptake inhibitor (SSRI) that the FDA has approved for generalized anxiety disorder and major depressive disorder. Interestingly, while many clients tolerate Lexapro much better than other SSRIs, some clients find the side effect spectrum to be unbearable:

  • Nausea (15-18%)
  • Diarrhea (6-14%)
  • Insomnia (7-14%)
  • Sexual dysfunction (9-14%)
  • Headaches (24%)

2. Cymbalta (duloxetine)

The FDA has approved Cymbalta, a serotonin-norepinephrine reuptake inhibitor (SNRI), to treat major depressive disorder, bipolar major depression, generalized anxiety disorder, and fibromyalgia. Moreover, this can be an excellent medication for some clients, especially those suffering from chronic pain conditions. However, other clients struggle to overcome an intolerable side effect spectrum:

  • Nausea (18-25%)
  • Dry mouth (11-14%)
  • Fatigue (5-11%)
  • Headaches (13-18%)
  • Drowsiness (9-11%)

3. Prozac (fluoxetine)

The FDA approved Prozac as the first-ever SSRI medication back in 1987. Prozac currently has indications to treat major depressive disorder, GAD, OCD, bulimia nervosa, and panic disorder. Notably, while it is one of the most widely prescribed SSRI medications in 2023, some clients struggle to tolerate this medication due to its side effect spectrum:

  • Nausea (21-29%)
  • Headache (21%)
  • Insomnia (10-33%)
  • Sexual dysfunction (54-58%, can even persist after discontinuation)
  • Tremor (3-13%)
SSRI vs IV Ketamine

4. Zoloft (sertraline)

The FDA approved Zoloft as the 2nd SSRI medication. Zoloft has indications to treat major depressive disorder, OCD, panic disorder, PTSD, and social anxiety disorder. Similarly, while this can be an incredible medication for some, others find the side effects too much to bear:

  • Sexual dysfunction (54-63%)
  • Diarrhea (20%)
  • Dizziness (12%)
  • Insomnia (20%)
  • Dry mouth (14%)

5. Effexor (venlafaxine)

The FDA has approved Effexor, an SNRI medication, with indications for major depressive disorder, generalized anxiety disorder, panic disorder, and social anxiety disorder. Effexor is often an excellent alternative to SSRI medications for some clients. On the other hand, others have difficulty coping with the side effect spectrum:

  • Nausea (30%)
  • Loss of appetite (8-22%)
  • Dizziness (16%)
  • Drowsiness (15%)
  • Insomnia (17-24%)

5. Wellbutrin (bupropion)

Wellbutrin provides clients with an alternative to the serotonergic medications discussed earlier. This medication works as a norepinephrine-dopamine reuptake inhibitor. It carries FDA indications for major depressive disorder, seasonal affective disorder, and smoking cessation. On a positive note, clients sometimes tolerate this medication better than the classic SSRI and SNRIs, but some still struggle to deal with its side effect spectrum:

  • Dry mouth (10-28%)
  • Insomnia (11-40%)
  • Headache (~ 34%)
  • Nausea (9-18%)
  • Increased heart rate (11%)
  • Sweating (5-22%)

6. Low-dose IV ketamine

Now, if you’ve been following us for a while, you likely know about the benefits of low-dose IV ketamine treatment for depression, PTSD, and anxiety. Nevertheless, like any other medication, ketamine does have certain side effects. In contrast to conventional treatment, this side effect spectrum usually lasts < 120 minutes and are typically self-limited

  • Feeling drowsy or sleepy (31%)
  • Mild dizziness (29%)
  • Mild, transient increases in blood pressure (average ~ 20mmHg systolic / 13mmHg diastolic)
  • Blurred vision (25%)
  • Feeling strange or unreal (24%)
  • Headache (19%)
  • Dry mouth (18%)

Frequently Asked Questions

The most common side effects of serotonergic medications include nausea, diarrhea, sexual dysfunction and headaches


These side effects are not commonly thought to last forever. Some side effects are most prominent at the beginning of treatment and subside over time. Other side effects are known as “dose-dependent,” meaning that they can be mitigated with lower doses of medications. Unfortunately, some of these side effects are intolerable and clients find themselves either asking to be weaned off of them, or stopping them abruptly (which we would not recommend). 

Unlike traditional psychiatric medications, low-dose IV ketamine treatments are usually very well tolerated with minimal side effect burden. If side effects do occur they are usually very mild and self-limited. In the case that side effects are uncomfortable, steps can be taken to ease this burden such as slowing the infusion, lowering the dose on subsequent infusions, or administering as-needed medications such as low doses of anti-nausea medications, anti-hypertensive medications or anti-anxiety medications. 

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