Can Antidepressants Trigger Psychosis? A Review of the Evidence

October 11, 2025 •

4 min read

While antidepressant-induced psychosis is rare, one retrospective review of adult psychiatric admissions found that 8.1% could be attributed to antidepressant-associated mania or psychosis [1.3.5]. The critical question remains: can antidepressants trigger psychosis in susceptible individuals?

Quick Summary

While rare, some antidepressants can trigger psychosis, particularly in individuals with underlying risk factors like a personal or family history of bipolar disorder [1.3.2, 1.2.3]. This reaction is often linked to misdiagnosis or the medication's effect on dopamine levels [1.4.4, 1.6.3].

Key Points

Rarity and Risk: Antidepressant-induced psychosis is a rare but serious adverse event, with one study noting it in a small percentage of psychiatric admissions [1.3.5].
Bipolar Disorder Link: The greatest risk factor is an undiagnosed bipolar disorder, where antidepressants can unmask the condition by triggering a manic or psychotic episode [1.2.3, 1.6.3].
Dopamine Hypothesis: The mechanism is often linked to the medication's effect on dopamine, with drugs like bupropion potentially posing a higher risk due to their dopaminergic action [1.4.4, 1.4.5].
Key Symptoms: Core symptoms to watch for include hallucinations, delusions, disorganized thought, and severe agitation [1.5.4, 1.5.5].
Immediate Management: If psychosis is suspected, the primary management step is to discontinue the antidepressant under medical supervision and potentially start an antipsychotic [1.7.4, 1.7.2].
Medication Differences: Older tricyclic antidepressants (TCAs) and agents that significantly impact dopamine may have a higher association with psychosis or delirium compared to SSRIs [1.2.4, 1.4.4].
Importance of Screening: Thorough patient screening for a personal or family history of bipolar disorder is crucial before initiating antidepressant therapy to mitigate risk [1.3.2, 1.6.3].

Understanding Treatment-Emergent Psychosis

While antidepressants are a cornerstone of treatment for depression and anxiety disorders, they can, in rare instances, be associated with the emergence of psychotic symptoms [1.3.5]. This phenomenon, often called treatment-emergent psychosis, involves experiencing symptoms like hallucinations or delusions after starting or increasing the dose of an antidepressant [1.5.2, 1.4.5]. It's crucial to understand that this is not a common side effect, but it is a serious one that requires immediate medical attention [1.3.2]. A key factor in this adverse event is the potential for misdiagnosis. Many individuals who experience this are later found to have an underlying bipolar disorder, where antidepressant monotherapy can trigger a manic or mixed episode with psychotic features [1.6.3, 1.6.7].

The Pharmacological Mechanisms

The way antidepressants work is by altering the balance of neurotransmitters in the brain, such as serotonin, norepinephrine, and dopamine [1.4.6]. The "dopamine hypothesis of psychosis" suggests that excessive dopamine activity in certain brain pathways is linked to psychotic symptoms like hallucinations and delusions [1.4.4]. Some antidepressants can influence dopamine levels, which may explain the potential to induce psychosis [1.4.4, 1.4.1]:

Bupropion: This medication is a norepinephrine and dopamine reuptake inhibitor. Its mechanism directly increases dopamine levels, which is thought to contribute to the risk of psychosis, although cases are uncommon [1.4.5, 1.4.4].
Venlafaxine (SNRI): At lower doses, it primarily blocks serotonin reuptake. At higher doses, it also blocks norepinephrine and even dopamine reuptake. This effect on dopamine at higher doses is believed to be a potential cause of psychotic symptoms [1.4.1].
SSRIs: While primarily targeting serotonin, some studies suggest that SSRIs may indirectly induce psychotic symptoms by mediating dopamine release in certain parts of the brain [1.4.2].
Tricyclic Antidepressants (TCAs): Older antidepressants like amitriptyline and clomipramine have been associated with a higher incidence of drug-induced delirium, which can include psychotic symptoms, partly due to their strong antimuscarinic (anticholinergic) properties [1.2.4].

Recognizing the Symptoms

It is vital for patients and their families to recognize the signs of psychosis. These symptoms represent a break from reality and can be distressing. Key symptoms include:

Hallucinations: Seeing, hearing, or feeling things that are not there [1.5.4, 1.5.5]. Auditory hallucinations (hearing voices) are common [1.5.5].
Delusions: Holding strong, false beliefs that are not based in reality, such as paranoia or delusions of persecution [1.5.4, 1.4.1].
Disorganized Thinking and Speech: Rapid, constant, or jumbled speech, or suddenly losing one's train of thought [1.5.5].
Agitation and Unusual Behavior: Severe restlessness, agitation, and behaving out of character [1.5.1, 1.5.2].

The Critical Role of Bipolar Disorder Misdiagnosis

A significant portion of cases of antidepressant-induced psychosis or mania occur in individuals with undiagnosed bipolar disorder [1.6.6]. A person might seek treatment during a depressive episode and be prescribed an antidepressant without a thorough screening for a history of mania or hypomania [1.6.3]. In these individuals, the antidepressant can "unmask" the latent bipolar disorder, triggering a switch into a manic episode which may include psychosis [1.2.3, 1.6.5]. For this reason, monotherapy with antidepressants is generally contraindicated for patients with Bipolar I disorder [1.6.7].


Risk Factor Category	Specific Factor	Relevance to Antidepressant-Induced Psychosis	Source(s)
Underlying Condition	Personal or family history of Bipolar Disorder	The single most significant risk factor. Antidepressants can unmask latent bipolarity, causing a switch to mania or psychosis.	[1.2.3, 1.3.2]
Underlying Condition	Pre-existing psychotic disorder	Patients with a history of psychosis (e.g., schizophrenia) may be more susceptible to symptom exacerbation.	[1.3.5]
Demographics	Female Sex	Studies have found that being female is associated with a higher risk of antidepressant-induced mania (AIM).	[1.3.1, 1.3.3]
Substance Use	Concomitant substance use	Using substances like cannabis or stimulants alongside antidepressants can increase the risk of inducing psychosis.	[1.2.3]
Medication Type	Dopaminergic Antidepressants	Drugs like Bupropion that directly increase dopamine activity may carry a higher risk based on the dopamine hypothesis of psychosis.	[1.4.4, 1.4.5]
Medication Type	Tricyclic Antidepressants (TCAs)	Older TCAs are more frequently implicated in causing delirium with psychotic features compared to newer agents.	[1.2.4]

Management and Treatment

If symptoms of psychosis emerge during antidepressant treatment, it is a medical emergency. The first and most critical step is to seek immediate medical evaluation. The management strategy typically involves:

Discontinuation of the Antidepressant: In many cases, discontinuing the offending medication leads to a rapid improvement in psychotic symptoms [1.7.4, 1.7.2].
Introduction of an Antipsychotic: An antipsychotic medication (such as olanzapine or risperidone) may be initiated to manage the acute psychotic symptoms [1.7.2, 1.7.1].
Re-evaluation of Diagnosis: The patient's diagnosis must be carefully reassessed. If an underlying bipolar disorder is identified, future treatment will likely involve mood stabilizers, with or without antidepressants [1.6.5, 1.7.7].

For an authoritative resource on mental health conditions, visit the National Institute of Mental Health (NIMH).

Conclusion

In conclusion, while antidepressants are vital medications for millions, they carry a rare but significant risk of triggering psychosis. This risk is not uniform across all patients or all medications. The most substantial predictor is an underlying, often undiagnosed, bipolar disorder, where antidepressants can induce a manic state with psychotic features [1.2.3, 1.6.3]. Other risk factors include a history of psychosis, female sex, and the use of certain types of antidepressants that have a more direct effect on dopamine pathways [1.3.1, 1.4.4]. Prompt recognition of symptoms like hallucinations and delusions, followed by immediate discontinuation of the antidepressant and a thorough diagnostic re-evaluation, is the cornerstone of managing this serious adverse event [1.7.4].

Frequently Asked Questions

It is very rare. One review of psychiatric hospital admissions attributed about 8.1% of cases to antidepressant-associated mania or psychosis, but this is within a population of individuals already requiring hospitalization [1.3.5]. In outpatient pediatric populations, some studies found no instances of induced psychosis [1.2.3].

There is some evidence that antidepressants with a direct effect on dopamine, like bupropion, may be associated with psychosis due to their mechanism of action [1.4.5]. Additionally, older tricyclic antidepressants (TCAs) have been linked to a higher incidence of drug-induced delirium with psychotic symptoms [1.2.4].

While less common than with some other classes, SSRIs can, in rare cases, induce psychosis or mania. This is often by indirectly affecting dopamine levels or by unmasking a latent bipolar disorder [1.4.2, 1.6.3]. One study noted the highest incidence of mania in children and adolescents was with fluoxetine (Prozac) [1.2.3].

The most significant risk factor is having a personal or family history of bipolar disorder. In these individuals, an antidepressant can trigger a manic episode that may include psychotic features [1.2.3, 1.3.2].

Early signs can include agitation, restlessness, insomnia, paranoia, and unusual changes in mood or behavior [1.5.1, 1.5.3]. The hallmark symptoms are hallucinations (seeing or hearing things that aren't there) and delusions (holding false, irrational beliefs) [1.5.4].

You should seek immediate medical attention. Do not stop taking your medication without consulting a doctor. Management typically involves stopping the antidepressant and may include starting an antipsychotic medication [1.7.4, 1.7.2].

Not at all. Antidepressants are effective for many people. This risk is rare and is most pronounced in individuals with specific risk factors, like a history of bipolar disorder [1.6.2]. A thorough evaluation and open communication with your doctor about your personal and family medical history can help mitigate this risk [1.7.7].