Psychotic depression is a severe mental illness characterized by a combination of major depressive disorder and psychosis. It is a particularly debilitating condition that affects a person’s thoughts, feelings, and behavior. People with psychotic depression experience hallucinations, delusions, and extreme sadness or hopelessness, which can make it difficult for them to function in daily life. If left untreated, it can lead to suicidal thoughts and behaviors. It is crucial to seek professional help if you suspect you or someone you know is experiencing psychotic depression.

Major Depressive Disorder With Psychotic Features Vs Schizoaffective Disorder

Major Depressive Disorder with Psychotic Features and Schizoaffective Disorder are both mental health disorders that have overlapping symptoms, but there are key differences that distinguish them.

Major Depressive Disorder with Psychotic Features is a type of depression typically characterized by intense sadness, a lack of energy, and a loss of interest in activities that were once enjoyable. In addition to these symptoms, individuals with Major Depressive Disorder with Psychotic Features also experience delusions and/or hallucinations. These delusions and hallucinations are typically mood-congruent, meaning that they match the general feeling of sadness and despair that accompanies depression. For instance, an individual with this disorder may have hallucinations of a deceased loved one, or delusional beliefs that they are guilty of some terrible wrongdoing. These symptoms typically only occur during an episode of depression and do not persist beyond the episode.

Schizoaffective Disorder is a mental health disorder that combines the symptoms of both schizophrenia and a mood disorder (usually Major Depressive Disorder or Bipolar Disorder). Individuals with Schizoaffective Disorder experience symptoms of psychosis (delusions, hallucinations, disorganized speech and behavior) in addition to the major mood disorder symptoms (depressive or manic episodes). Unlike Major Depressive Disorder with Psychotic Features, the symptoms of Schizoaffective Disorder can occur independent of a mood episode. Additionally, the delusions and hallucinations experienced by individuals with Schizoaffective Disorder may not be mood-congruent.

In summary, the main difference between Major Depressive Disorder with Psychotic Features and Schizoaffective Disorder is that Schizoaffective Disorder is a more complex disorder that combines symptoms of schizophrenia and a mood disorder, while Major Depressive Disorder with Psychotic Features only involves major depressive disorder symptoms with additional psychosis during the episode.

What are Depression and Bipolar with Psychotic Features?

Psychotic depression

Medical condition
Psychotic depression
Other names Depressive psychosis
Grieving shadow.jpg
A drawing that attempts to capture the sadness, loneliness, and detachment from reality, as described by patients with psychotic depression
Specialty Psychiatry
Symptoms Hallucinations, delusions, anhedonia, psychomotor retardation, sleep problems,
Complications Suicide, self-harm, risk of relapse of psychotic depression
Usual onset 20-40 years old
Duration Days to weeks, sometimes longer
Diagnostic method Clinical interview
Differential diagnosis Schizoaffective disorder, schizophrenia, personality disorders, dissociative disorders
Treatment Medication, cognitive behavioral therapy
Medication Anti-depressants, anti-psychotics

Psychotic depression, also known as depressive psychosis, is a major depressive episode that is accompanied by psychotic symptoms. It can occur in the context of bipolar disorder or major depressive disorder. It can be difficult to distinguish from schizoaffective disorder, a diagnosis that requires the presence of psychotic symptoms for at least two weeks without any mood symptoms present. Unipolar psychotic depression requires that psychotic symptoms occur during severe depressive episodes, although residual psychotic symptoms may also be present in between episodes (eg: during remission, mild depression…). Diagnosis using the DSM-5 involves meeting the criteria for a major depressive episode, along with the criteria for “mood-congruent or mood-incongruent psychotic features” specifier.

Signs and symptoms

Individuals with psychotic depression experience the symptoms of a major depressive episode, along with one or more psychotic symptoms, including delusions and/or hallucinations. Delusions can be classified as mood congruent or incongruent, depending on whether or not the nature of the delusions is in keeping with the individual’s mood state. Common themes of mood congruent delusions include guilt, persecution, punishment, personal inadequacy, or disease. Half of patients experience more than one kind of delusion. Delusions occur without hallucinations in about one-half to two-thirds of patients with psychotic depression. Hallucinations can be auditory, visual, olfactory (smell), or tactile (touch), and are congruent with delusional material. Affect is sad, not flat. Severe anhedonia, loss of interest, and psychomotor retardation are typically present.


Psychotic symptoms tend to develop after an individual has already had several episodes of depression without psychosis. However, once psychotic symptoms have emerged, they tend to reappear with each future depressive episode. The prognosis for psychotic depression is not considered to be as poor as for schizoaffective disorders or primary psychotic disorders. Still, those who have experienced a depressive episode with psychotic features have an increased risk of relapse and suicide compared to those without psychotic features, and they tend to have more pronounced sleep abnormalities.

Family members of those who have experienced psychotic depression are at increased risk for both psychotic depression and schizophrenia.

Most patients with psychotic depression report having an initial episode between the ages of 20 and 40. As with other depressive episodes, psychotic depression tends to be episodic, with symptoms lasting for a certain amount of time and then subsiding. While psychotic depression can be chronic (lasting more than 2 years), most depressive episodes last less than 24 months. A study conducted by Kathleen S. Bingham found that patients receiving appropriate treatment for psychotic depression went into “remission”. They reported a quality of life similar to that of people without PD.


There are a number of biological features that may distinguish psychotic depression from non-psychotic depression. The most significant difference may be the presence of an abnormality in the hypothalamic pituitary adrenal axis (HPA). The HPA axis appears to be dysregulated in psychotic depression, with dexamethasone suppression tests demonstrating higher levels of cortisol following dexamethasone administration (i.e. lower cortisol suppression). Those with psychotic depression also have higher ventricular-brain ratios than those with non-psychotic depression.


Differential diagnosis

See also: Depression (differential diagnoses)

Psychotic symptoms are often missed in psychotic depression, either because patients do not think their symptoms are abnormal or they attempt to conceal their symptoms from others. On the other hand, psychotic depression may be confused with schizoaffective disorder. Due to overlapping symptoms, differential diagnosis includes also dissociative disorders.


Several treatment guidelines recommend pharmaceutical treatments that include either the combination of a second-generation antidepressant and atypical antipsychotic or tricyclic antidepressant monotherapy or electroconvulsive therapy (ECT) as the first-line treatment for unipolar psychotic depression.

There is no evidence for or against the use of mifepristone.

Combined antidepressant and antipsychotic medications

There is some evidence indicating that combination therapy with an antidepressant plus an antipsychotic is more effective in treating psychotic depression than either antidepressant treatment alone or placebo. In the context of psychotic depression, the following are the most well-studied antidepressant/antipsychotic combinations:


  • Amitriptyline/perphenazine
  • Amitriptyline/haloperidol


  • Venlafaxine/quetiapine
  • Olanzapine/fluoxetine
  • Olanzapine/sertraline

Antidepressant medications

There is insufficient evidence to determine if treatment with an antidepressant alone is effective. Tricyclic antidepressants may be particularly dangerous, because overdosing has the potential to cause fatal cardiac arrhythmias.

Antipsychotic medications

There is insufficient evidence to determine if treatment with antipsychotic medications alone is effective. Olanzapine may be an effective monotherapy in psychotic depression, although there is evidence that it is ineffective for depressive symptoms as a monotherapy; and olanzapine/fluoxetine is more effective. Quetiapine monotherapy may be particularly helpful in psychotic depression since it has both antidepressant and antipsychotic effects and a reasonable tolerability profile compared to other atypical antipsychotics. The current drug-based treatments of psychotic depression are reasonably effective but can cause side effects, such as nausea, headaches, dizziness, and weight gain.

Electroconvulsive therapy (ECT)

In modern practice of ECT a therapeutic clonic seizure is induced by electric current via electrodes placed on a person under general anesthesia. Despite much research the exact mechanism of action of ECT is still not known. ECT carries the risk of temporary cognitive deficits (e.g., confusion, memory problems), in addition to the burden of repeated exposures to general anesthesia.


Efforts are made to find a treatment which targets the proposed specific underlying pathophysiology of psychotic depression. A promising candidate was mifepristone, which by competitively blocking certain neuro-receptors, renders cortisol less able to directly act on the brain and was thought to therefore correct an overactive HPA axis. However, a Phase III clinical trial, which investigated the use of mifepristone in PMD, was terminated early due to lack of efficacy.

Transcranial magnetic stimulation (TMS) is being investigated as an alternative to ECT in the treatment of depression. TMS involves the administration of a focused electromagnetic field to the cortex to stimulate specific nerve pathways.

Research has shown that psychotic depression differs from non-psychotic depression in a number of ways: potential precipitating factors, underlying biology, symptomatology beyond psychotic symptoms, long-term prognosis, and responsiveness to psychopharmacological treatment and ECT.


The long-term outcome for psychotic depression is generally poorer than for non-psychotic depression.


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