What are the side effects of fluoxetine (Prozac)?

From the Guidelines

Prozac (fluoxetine) commonly causes side effects including nausea, headache, insomnia, drowsiness, anxiety, nervousness, and sexual dysfunction, as reported in the most recent study 1. These side effects occur because Prozac increases serotonin levels in the brain by blocking its reuptake, which affects multiple body systems beyond just mood regulation. Some key points to consider when prescribing Prozac include:

• Starting at a lower dose and gradually increasing can sometimes minimize initial side effects, as suggested by the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1.
• Side effects often improve after the first few weeks as the body adjusts to the medication.
• If experiencing severe or persistent side effects, patients should contact their healthcare provider rather than stopping the medication abruptly, as this can cause withdrawal symptoms.
• The most commonly reported adverse events were constipation, diarrhea, dizziness, headache, insomnia, nausea, sexual adverse events, and somnolence, as reported in the study 1.
• Nausea and vomiting were the most common reasons for discontinuation in efficacy studies.
• Paroxetine had higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline, as reported in the study 1.
• Selective serotonin reuptake inhibitors resulted in an increased risk for nonfatal suicide attempts, as reported in the study 1.
• The initial dosage of Prozac is 10 mg every other morning, with a maximum dosage of 20 mg every morning, as recommended in the guidelines for managing Alzheimer's disease 1. It is essential to carefully monitor patients for potential side effects and adjust the treatment plan accordingly to minimize the risk of adverse events and optimize the benefit-to-harm ratio, as emphasized in the clinical practice guideline 1.

From the FDA Drug Label

ADVERSE REACTIONS Multiple doses of Prozac had been administered to 10,782 patients with various diagnoses in US clinical trials as of May 8,1995. In addition, there have been 425 patients administered Prozac in panic clinical trials. Adverse events were recorded by clinical investigators using descriptive terminology of their own choosing Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a limited (i.e., reduced) number of standardized event categories. 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 An event was considered treatment–emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. It is important to emphasize that events reported during therapy were not necessarily caused by it The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the population studied 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) for the treatment of major depressive disorder, OCD, and bulimia in US controlled clinical trials and panic disorder in US plus non–US controlled trials 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 Table 3 provides combined data for the pool of studies that are provided separately by indication in Table 2. 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
• 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 include:

• Abnormal bleeding: increased risk of bleeding events, especially when combined with other medications like aspirin, nonsteroidal anti-inflammatory drugs, or warfarin 2
• Anxiety and insomnia: reported in 12% to 16% of patients treated with Prozac for major depressive disorder, and in 28% of patients treated with Prozac for OCD 2
• Altered appetite and weight: significant weight loss, especially in underweight patients, and decreased appetite reported in 11% of patients treated with Prozac for major depressive disorder 2
• Activation of mania/hypomania: reported in 0.1% of patients treated with Prozac for major depressive disorder, and in 0.8% of patients treated with Prozac for OCD 2
• Hyponatremia: may occur as a result of treatment with Prozac, especially in elderly patients or those taking diuretics 2
• Seizures: reported in 0.1% of patients treated with Prozac for major depressive disorder 2
• Diarrhea: reported in 10% of patients taking Prozac Weekly, compared to 3% of patients taking placebo or 5% of patients taking Prozac 20 mg daily 2
• Thirst, hyperkinesia, agitation, personality disorder, epistaxis, urinary frequency, and menorrhagia: reported in pediatric patients treated with Prozac 2

From the Research

Side Effects of Prozac

• The selective serotonin reuptake inhibitor (SSRI) Prozac (fluoxetine) has been reported to have several side effects, including:
  • Premature birth, neonatal cardiovascular abnormalities, and pulmonary hypertension in children whose mothers used SSRIs during pregnancy 3
  • Increased risk for suicidal behavior in adolescents 3
  • Paradoxical anxiety- and depression-like features in later life of rats and mice exposed to fluoxetine during neonatal and adolescent stages 3
• Cardiovascular side effects of fluoxetine include:
  • Dysrhythmia (atrial fibrillation and bradycardia) and syncope associated with fluoxetine treatment and overdose 4
  • Cardiodepressant and vasodilatory effects in isolated heart preparations and vessels of rats and rabbits 4
  • Potential adverse cardiovascular effects, including atherogenesis, cardiac pathologies, and cerebromicrovascular impairment, particularly in geriatric patients 5
• Other side effects of fluoxetine include:
  • Alteration of Ca(2+) homeostatic cascades and up-regulation and editing of astrocytic genes 6
  • Modification of neural activity related to risk taking and reward processing, including reduced neural response to increasing risk in lateral orbitofrontal cortex and decreased responsiveness to rewarding outcomes in midbrain regions 7