From the Guidelines
Prozac (fluoxetine) side effects occur in a significant percentage of patients, with the most common being nausea, headache, insomnia, and sexual dysfunction, affecting up to 20-30% of patients.
Common Side Effects
- Nausea and vomiting: most common reasons for discontinuation in efficacy studies
- Headache: commonly reported adverse event
- Insomnia: commonly reported adverse event
- Sexual adverse events: including sexual dysfunction, affecting up to 20-30% of patients 1
- Diarrhea: commonly reported adverse event, although less common than with sertraline
- Dizziness: commonly reported adverse event
- Somnolence: commonly reported adverse event, although less common than with trazodone
Severe Side Effects
- Suicidality: SSRIs, including fluoxetine, are associated with an increased risk for suicide attempts compared with placebo, with an odds ratio of 2.25 [CI, 3.3 to 4.6] 1
- Sexual Dysfunction: fluoxetine has a higher rate of sexual adverse events than bupropion, but a lower rate than paroxetine 1
Monitoring and Management
Regular monitoring of patients on fluoxetine is crucial, particularly during the first 1-2 weeks of initiation of therapy, to assess for adverse effects and suicidal thoughts and behaviors 1.
From the FDA Drug Label
In the tables and tabulations that follow, COSTART Dictionary terminology has been used to classify reported adverse events. The stated frequencies represent the proportion of individuals who experienced, at least once, a treatment–emergent adverse event of the type listed Incidence in major depressive disorder, OCD, bulimia, and panic disorder placebo–controlled clinical trials (excluding data from extensions of trials) — Table 2 enumerates the most common treatment–emergent adverse events associated with the use of Prozac (incidence of at least 5% for Prozac and at least twice that for placebo within at least 1 of the indications) Table 3 enumerates treatment–emergent adverse events that occurred in 2% or more patients treated with Prozac and with incidence greater than placebo who participated in US major depressive disorder, OCD, and bulimia controlled clinical trials and US plus non–US panic disorder controlled clinical trials Other adverse events in pediatric patients (children and adolescents) — Treatment–emergent adverse events were collected in 322 pediatric patients (180 fluoxetine–treated, 142 placebo–treated) The overall profile of adverse events was generally similar to that seen in adult studies, as shown in Tables 2 and 3 However, the following adverse events (excluding those which appear in the body or footnotes of Tables 2 and 3 and those for which the COSTART terms were uninformative or misleading) were reported at an incidence of at least 2% for fluoxetine and greater than placebo: thirst, hyperkinesia, agitation, personality disorder, epistaxis, urinary frequency, and menorrhagia The most common adverse event (incidence at least 1% for fluoxetine and greater than placebo) associated with discontinuation in 3 pediatric placebo–controlled trials (N=418 randomized; 228 fluoxetine–treated; 190 placebo–treated) was mania/hypomania (1. 8% for fluoxetine–treated, 0% for placebo–treated). In these clinical trials, only a primary event associated with discontinuation was collected. Events observed in Prozac Weekly clinical trials — Treatment–emergent adverse events in clinical trials with Prozac Weekly were similar to the adverse events reported by patients in clinical trials with Prozac daily In a placebo–controlled clinical trial, more patients taking Prozac Weekly reported diarrhea than patients taking placebo (10% versus 3%, respectively) or taking Prozac 20 mg daily (10% versus 5%, respectively).
The side effects of Prozac (fluoxetine) and their percentages are:
- Anxiety and Insomnia:
- Anxiety: 12% to 16% of patients treated with Prozac and 7% to 9% of patients treated with placebo reported anxiety, nervousness, or insomnia in US placebo–controlled clinical trials for major depressive disorder 2
- Insomnia: 28% of patients treated with Prozac and in 22% of patients treated with placebo in US placebo–controlled clinical trials for OCD 2
- Anxiety: 14% of patients treated with Prozac and in 7% of patients treated with placebo in US placebo–controlled clinical trials for OCD 2
- Insomnia: 33% of patients treated with Prozac 60 mg, and 13% of patients treated with placebo in US placebo–controlled clinical trials for bulimia nervosa 2
- Altered Appetite and Weight:
- Anorexia (decreased appetite): 11% of patients treated with Prozac and 2% of patients treated with placebo in US placebo–controlled clinical trials for major depressive disorder 2
- Weight loss: 1.4% of patients treated with Prozac and in 0.5% of patients treated with placebo in US placebo–controlled clinical trials for major depressive disorder 2
- Activation of Mania/Hypomania:
- Mania/hypomania: 0.1% of patients treated with Prozac and 0.1% of patients treated with placebo in US placebo–controlled clinical trials for major depressive disorder 2
- Mania/hypomania: 0.8% of patients treated with Prozac and no patients treated with placebo in US placebo–controlled clinical trials for OCD 2
- Hyponatremia:
- Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including Prozac 2
- Other side effects:
- Thirst: at least 2% for fluoxetine and greater than placebo in pediatric patients 2
- Hyperkinesia: at least 2% for fluoxetine and greater than placebo in pediatric patients 2
- Agitation: at least 2% for fluoxetine and greater than placebo in pediatric patients 2
- Personality disorder: at least 2% for fluoxetine and greater than placebo in pediatric patients 2
- Epistaxis: at least 2% for fluoxetine and greater than placebo in pediatric patients 2
- Urinary frequency: at least 2% for fluoxetine and greater than placebo in pediatric patients 2
- Menorrhagia: at least 2% for fluoxetine and greater than placebo in pediatric patients 2
- Diarrhea: 10% of patients taking Prozac Weekly reported diarrhea compared to 3% of patients taking placebo and 5% of patients taking Prozac 20 mg daily in a placebo–controlled clinical trial 2
From the Research
Side Effects of Prozac (Fluoxetine)
The side effects of Prozac (fluoxetine) can be categorized into major and minor adverse reactions. According to 3, the major side effects include:
- Serotonin syndrome
- Cardiovascular complications
- Extrapyramidal side effects such as akathisia, dyskinesias, and parkinsonian-like syndromes
- Increased risk of suicidality
- Fluoxetine-induced mania and hypomania
- Seizures
- Sexual disorders
Minor Side Effects
The minor side effects of fluoxetine include:
- Allergic reactions
- Stuttering
- Hematological changes
- Psoriasis
- Inappropriate secretion of the antidiuretic hormone 3
Common Side Effects
A study published in 4 found that the most common side effects of selective serotonin reuptake inhibitor antidepressants, including fluoxetine, were:
- Sexual functioning (reported by 38% of patients)
- Sleepiness
- Weight gain
Percentage of Patients Experiencing Side Effects
According to 4, 38% of patients reported experiencing a side effect as a result of taking a selective serotonin reuptake inhibitor antidepressant, including fluoxetine. However, only 25% of the side effects were considered "very bothersome" or "extremely bothersome".
Safety and Side Effect Profile
5 states that fluoxetine is generally safe and well-tolerated, with common adverse events reported with the recommended dose of 20 mg/day being referable to the gastrointestinal system and the nervous system. The approved dose range is up to 80 mg/day, and when higher doses are used, adverse events are more common.
Comparison of Side Effects with Other Treatments
A study published in 6 found that the combination of fluoxetine with cognitive-behavioral therapy (CBT) offered the most favorable tradeoff between benefit and risk for adolescents with major depressive disorder, with response rates of 71.0% for fluoxetine with CBT, compared to 60.6% for fluoxetine alone, 43.2% for CBT alone, and 34.8% for placebo.