Starting Prozac Versus Restarting Prozac: Efficacy And Side Effects

In our latest question and answer, the pharmacist compares the side effects and effectiveness of Prozac when starting for the first time versus restarting.


Good evening. My PCP wants me to start taking Prozac (10mg) for 2 weeks then up to 20 mg. For about 10 years, I had taken 40mg of Prozac, 150 mg of Wellbutrin, and 1 mg of Klonopin for anxiety/panic attacks. I currently take .05 mg of Klonopin at night, unless my anxiety is worse, and will take another 0.25mg during the day. I'm worried about what effect taking the Prozac will have on me. Obviously, with anxiety, I worry about taking just about everything, especially new things. Do you think I would have any adverse reactions since I had taken it in the past? I forgot to mention I've been off the Prozac and Wellbutrin for about 2 years. My anxiety is worse however I'm still able to function. Thank you very much for your advice and I look forward to hearing from you.

Asked by Chefshanda4 On Apr 17, 2021

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Apr 26, 2021
Last updated Aug 12, 2022

Key points

  • It can be difficult to predict if you will respond as well to the same antidepressant (e.g. Prozac) again after stopping and starting it again after a long period of time.
  • Studies show mixed results, with some showing a good response to reinitiation while others have shown a diminished response.
  • The side effects, and the rate at which they occur, seem to be similar for those just starting out on Prozac and in those that are restarting after stopping for a period of time.

Hello and thanks for writing to us!

When it comes to the potential adverse reactions (i.e. side effects) of SSRIs (selective serotonin reuptake inhibitors) like Prozac (fluoxetine), they are well-documented. Potential side effects include:

  • Sexual dysfunction (~15-20%)
  • Drowsiness (~17%)
  • Weight gain (~12%)
  • Insomnia (~11%)
  • Anxiety (~11%)
  • Headache (~10%)
  • Gastrointestinal (~10%)

There isn't, unfortunately, much data available regarding the situation you're asking about (i.e. having been on Prozac before and restarting after a period of time, will the side effects you experience be the same?).

Restarting Prozac After Stopping - Efficacy

There have been several studies examining the question of how an individual responds (in terms of efficacy) to reinitiating (i.e. starting again) an antidepressant they have been on before, and the results are mixed.

One study concluded the following:

This study suggests that patients who, after an initial response to fluoxetine [Prozac], relapse upon switching to placebo have a relatively high probability of responding to the reinitiation of fluoxetine treatment
Psychother Psychosom . Jul-Aug 2002;71(4):195-9

Other studies, however, have noted that it isn't uncommon for prior responders to have a decrease in efficacy. One such study states the following:

Our review suggests that a stable response to antidepressants after reinstatement cannot be assumed in all patients.
Psychother Psychosom. 2018 Sep; 87(4): 268–275

The overall point here is that it can be hard to predict if restarting Prozac after stopping it will bring about a positive response. Some may, while others won't (or not as strong as before).

Now, you asked about side effects.

Side Effects Restarting Prozac

All the studies I've seen that involve SSRIs (like Prozac) haven't noted any significant difference in the rate at which side effects occur when comparing initiating of therapy, to restarting therapy after a long period of time.

So, in your situation, having been off Prozac for two years, and restarting now, I wouldn't think you'd be any more or less at risk for experiencing the side effects commonly associated with the drug. Two years is a long time too, and you won't have any of the previous drugs in your system.

My recommendation to you would be to be prepared for the fact that you are most likely at the same risk for side effects as most individuals starting Prozac for the first time. Fortunately, if any do occur, they tend to decrease in severity after a few weeks/months.

Final Words

Lastly, you asked about Klonopin. There is a moderate interaction between it and Prozac.

Prozac can inhibit the metabolism of clonazepam. resulting in increased concentrations. In other words, it may make its effects more pronounced. You may want to start at a low dose of Klonopin when taking with Prozac to see how you respond.

Thanks again for reaching out to us!


  • Treatment approaches to major depressive disorder relapse. Part 2: reinitiation of antidepressant treatment, PubMed
  • Failure to Respond after Reinstatement of Antidepressant Medication: A Systematic Review, PubMed

About the Pharmacist

Dr. Brian Staiger, PharmD

Dr. Brian has been practicing pharmacy for over 11 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication-related questions! Feel free to send him an email at! You can also connect with Dr. Brian Staiger on LinkedIn.

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