Can Antidepressant Medications Cause Psychosis?

A subscriber to my YouTube channel 15-Minute Pharmacology recently asked if a common type of antidepressant medication can cause psychosis:

“Can SSRI’s bring on a psychotic episode? My good friend has become acutely unwell and completely psychotic after being put on SSRIs twice.”


The SSRI Medications

Selective Serotonin Reuptake Inhibitor or SSRI medications are used to treat major depressive disorder, generalized anxiety disorder, post-traumatic stress disorder, or obsessive-compulsive disorder. (The fact that this single type of medication is being used to treat so many seemingly different diagnoses suggests that our diagnostic system needs an overhaul – but that’s a discussion for another day).

These illnesses are relatively common, and SSRI medications are not only reasonably effective in treating them, they are also relatively safe as compared to other medications. It’s no surprise therefore that they are among the most widely prescribed medications in the world. Like any medication, however, they have side effects. And although it’s rare, psychosis can be one of them.


The Psychosis Risk of SSRI Medications

In 1988, fluoxetine (Prozac) became the first SSRI medication to be released in the US after being approved by the FDA. Several other SSRI medications were subsequently approved and released. There have been reports of hallucinations associated with many of these other SSRI medications since. These include:

  • Visual hallucinations with sertraline (Marcon et al., 2004).
  • Visual hallucinations and psychotic symptoms during treatment with selective serotonin reuptake inhibitors: Is the sigma receptor involved? (Schuld et al., 2000).
  • Factors associated with complex visual hallucinations during antidepressant treatment (Cancelli et al., 2004).
  • Escitalopram-related visual and auditory hallucination in a non-dementia patient with depression (Lai, 2012).
  • Visual and auditory hallucinations during normal use of paroxetine for treatment of major depressive disorder (Monji et al., 2011).
  • Citalopram-induced hallucinations and delusions in a young adult (Capaldi & Carr, 2010).
  • Visual and auditory hallucinations associated with citalopram treatment (Waltereit et al., 2013).


How Can SSRI Medications Cause Psychosis?

The mechanism by which these drugs can provoke hallucinations is not known. But several theories have been proposed.

According to one theory, people with especially sensitivity serotonin receptors might experience hallucinations from SSRI treatment as the medication will raise serotonin levels around those receptors.

Another theory revolves around a protein known as the sigma receptor. Sigma receptors are present in many brain regions and are involved in the regulation of cognition, mood, and perception. SSRI interactions with sigma receptors might explain why some SSRI medications might cause psychosis while other SSRI medications might relieve psychosis.

Yet another theory concerns the brain’s dopamine system. The most common neurochemical pathway to psychosis is overstimulation of this system. A 2002 study found high levels of dopamine metabolites among people who experienced mania or psychosis as a side effect of SSRI treatment.


Provoking Mania

Bipolar disorder is characterized by episodes of depression and mania. Most episodes of mania involve elevated mood, high levels of energy, decreased need for sleep, and grandiose ideas. Symptoms of psychosis are common during episodes of mania.

Episodes of depression are also common in people with bipolar disorder. In fact, for the average person with bipolar disorder, it’s more likely that a mood episode will be a depressed one.

Treating depression in bipolar disorder is complicated because SSRI medications and similar antidepressants can also provoke episodes of mania instead of just treating the depression – and psychosis can often accompany mania.

So, another potential explanation for the link between SSRI medications and psychosis is the possibility that they can provoke episodes of mania in people with bipolar disorder.


A Rare Side Effect

Although psychosis from SSRI medications can happen, it’s very uncommon.

When fluoxetine (Prozac) became the first SSRI medication to be approved for use in the United States in 1988, unpublished pre-market data suggested that hallucinations were an infrequent side effect of the medication. A 1998 report seemed to support this. The report estimated that about 26 million patients had used fluoxetine, with 838 (0.0032%) cases of hallucinations reported. On the other hand, a 2001 review of 533 patients ill enough to require psychiatric hospitalization identified 43 people (8.1%) who were admitted because of antidepressant-associated mania or psychosis.  Most of those hospital admissions, however, were from people with bipolar disorder who experienced an activation of mania from SSRI treatment.]


Treating Depression Without SSRI Medications

We’ve seen in this post that SSRI medications might provoke episodes of mania or manic psychosis in people with bipolar disorder and might also directly trigger psychosis in others. But in addition to these side effects, SSRI medications have side effects that are more common but less dramatic. There’s no free lunch, as they say.

There is no doubt that SSRI medications can help many people. But there are many others who can’t take them. This begs the question: Are there good alternatives to SSRI medications?

The answer is: Yes. Absolutely yes.

Not all antidepressant or anti-anxiety medications impact the serotonin system. It’s possible to treat these conditions by targeting neurotransmitters like norepinephrine, dopamine, GABA, or glutamate. Brain stimulation treatments like electroconvulsive therapy or transcranial magnetic stimulation can also be effective.

It is also possible to treat depression, anxiety, post-traumatic stress disorder, or obsessive-compulsive disorder without any medications at all. Evidence-based psychotherapies can be as effective as medications in many cases. These non-medication treatments are so good (and side-effect free) that people like Dr Joel Paris of McGill University suggests not using medications as initial treatments in cases of moderate depression.

Conditions like anxiety or depression have many different causes. This means that they can be effectively treated in many different ways. Prescribing medications has never been and should never become the primary function of psychiatry. The physician’s goal is always to help people move from illness to health as quickly and as completely as possible. Medication is just one tool out of many that can help then on their journey to recovery.



This article summarizes the results and conclusions of articles published in the medical literature. It is for general information. It is not a substitute for medical advice, and readers are admonished not to enact or change treatments based on this article. Always seek the advice of your doctor before starting or changing treatment.

The thoughts, views, and opinions expressed in this article are my own and do not reflect or represent the policy or position of Northeast Ohio Medical University



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