Can fluoxetine (Prozac) induce psychosis?

From the Guidelines

Fluoxetine (Prozac) can potentially induce psychosis in rare cases, and its use requires careful monitoring, especially in patients with bipolar disorder or those taking other serotonergic medications. This selective serotonin reuptake inhibitor (SSRI) antidepressant typically helps treat depression, anxiety, and other mental health conditions, but paradoxical reactions can occur. The risk of Prozac-induced psychosis is higher in patients with bipolar disorder who haven't been diagnosed or properly treated with mood stabilizers, as SSRIs can trigger manic episodes with psychotic features, as noted in the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1. Other risk factors include high doses, rapid dose increases, or combining Prozac with other serotonergic medications, such as monoamine oxidase inhibitors (MAOIs), which is contraindicated due to the increased risk of serotonin syndrome 1.

Some key points to consider when prescribing fluoxetine include:

• Starting with a low dose and increasing it slowly to minimize the risk of adverse effects, especially in the first 24 to 48 hours after dosage changes 1
• Monitoring for symptoms of serotonin syndrome, such as anxiety, agitation, and changes in mental status 1
• Avoiding concomitant administration of fluoxetine with other medications that can interact with it, such as drugs that prolong the QT interval or are metabolized by CYP2D6 1
• Being aware of the potential for discontinuation syndrome, which can occur when fluoxetine is stopped abruptly or the dose is reduced too quickly 1

Symptoms of medication-induced psychosis may include hallucinations, delusions, disorganized thinking, and agitation. If someone experiences these symptoms while taking Prozac, they should contact their healthcare provider immediately, as dose adjustment, medication change, or additional treatment may be necessary. The mechanism likely involves excessive serotonin activity in certain brain regions, disrupting normal neurotransmitter balance. This rare side effect underscores the importance of careful monitoring when starting or adjusting antidepressant medications, and highlights the need for medical education, training, and experience to safely and effectively prescribe these medications 1.

From the FDA Drug Label

Among 633 adult patients who overdosed on fluoxetine hydrochloride alone, 34 resulted in a fatal outcome, 378 completely recovered, and 15 patients experienced sequelae after overdosage, including abnormal accommodation, abnormal gait, confusion, unresponsiveness, nervousness, pulmonary dysfunction, vertigo, tremor, elevated blood pressure, impotence, movement disorder, and hypomania The most common signs and symptoms associated with non–fatal overdosage were seizures, somnolence, nausea, tachycardia, and vomiting. Other important adverse events reported with fluoxetine overdose (single or multiple drugs) include coma, delirium, ECG abnormalities (such as QT interval prolongation and ventricular tachycardia, including torsades de pointes–type arrhythmias), hypotension, mania, neuroleptic malignant syndrome–like events, pyrexia, stupor, and syncope Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls More severe and/or acute cases have been associated with hallucination, syncope, seizure, coma, respiratory arrest, and death.

Fluoxetine and Psychosis: The FDA drug label does not directly answer whether fluoxetine can induce psychosis. However, it does mention that hallucination is a possible symptom of severe hyponatremia, a condition that may occur as a result of treatment with fluoxetine 2. Additionally, the label reports delirium as an adverse event associated with fluoxetine overdose 2. While these events are related to the psychiatric realm, they do not directly imply that fluoxetine can induce psychosis.

• Key points:
  • Hallucination is a possible symptom of severe hyponatremia associated with fluoxetine treatment.
  • Delirium is an adverse event reported with fluoxetine overdose.
  • The label does not provide direct evidence that fluoxetine can induce psychosis. Therefore, based on the available information, no conclusion can be drawn about the ability of fluoxetine to induce psychosis 2, 2.

From the Research

Fluoxetine and Psychosis

• The relationship between fluoxetine (Prozac) and psychosis is complex, with some studies suggesting a potential link between the two 3, 4, 5.
• A study published in 2009 found that fluoxetine monotherapy can lead to a decrease in psychotic-like symptoms in patients with non-psychotic major depressive disorder 5.
• However, another study published in 2011 found that bupropion, an antidepressant with some similar mechanisms to fluoxetine, may cause or worsen psychosis in selected subpopulations, particularly at higher doses or in individuals with preexisting psychotic symptoms 4.
• A review of medication-induced psychotic disorder published in 2022 noted that various medications, including steroids, antiepileptic drugs, and antimalarial drugs, can induce psychosis, but did not specifically mention fluoxetine 3.
• A study published in 2016 found that selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants that includes fluoxetine, did not induce psychotic symptoms in children and adolescents 6.
• A study published in 2017 discussed the use of antipsychotic drugs to manage psychosis, but did not address the potential for fluoxetine to induce psychosis 7.

Key Findings

• Fluoxetine may decrease psychotic-like symptoms in patients with non-psychotic major depressive disorder 5.
• Certain medications, including bupropion, may cause or worsen psychosis in selected subpopulations 4.
• The relationship between fluoxetine and psychosis is not fully understood and requires further research 3, 4, 5.