Depression with psychosis overview symptoms diagnosis and treatment

Definition and diagnostic criteria

Depression with psychosis, clinically known as major depressive disorder with psychotic features (often referred to as psychotic depression), occurs when a major depressive episode includes psychotic symptoms. The psychotic symptoms appear during the mood episode and tend to reflect the mood state (mood-congruent) but can also be mood-incongruent. This combination is distinct from schizophrenia or schizoaffective disorder, where psychotic symptoms may appear outside of mood episodes or follow a different course.

Key diagnostic principles include:

• The presence of a major depressive episode: at least five of the core symptoms of depression (depressed mood, anhedonia, significant weight or sleep change, psychomotor changes, fatigue, concentration problems, feelings of worthlessness or excessive guilt, or recurrent thoughts of death) over a two-week period, causing clinically significant distress or impairment.
• Concurrent psychotic features: delusions or hallucinations that occur during the depressive episode. These psychotic symptoms may be mood-congruent (consistent with depressive themes such as guilt or worthlessness) or mood-incongruent (not clearly tied to depressive themes).
• Time course: psychotic symptoms are present during depressive episodes and typically remit when the depressive mood improves (though treatment may be needed to achieve remission).
• Exclusion of other causes: medical conditions, substances, or other psychiatric illnesses that better explain the psychosis or mood symptoms are ruled out, and there is no history suggesting a primary psychotic disorder alone.

In ICD-11 terms, this is described as a depressive episode with psychotic features, with the psychotic symptoms occurring during the depressive episode. A careful clinical assessment is essential to distinguish this condition from other psychotic or mood disorders and to guide appropriate treatment.

Symptoms and signs

Depressive symptoms (typical of a major depressive episode)

• Persistent sad, empty, or hopeless mood most of the day
• Marked loss of interest or pleasure in activities (anhedonia)
• Significant changes in appetite or weight
• Sleep disturbances (insomnia or hypersomnia)
• Fatigue or loss of energy
• Difficulty concentrating, making decisions, or remembering things
• Feelings of worthlessness, excessive guilt, or self-blame
• Psychomotor agitation or retardation
• Recurrent thoughts of death or suicide, or suicide attempts

Psychotic symptoms during depressive episodes

• Delusions: fixed false beliefs that are not shared by others (for example, beliefs of being punished, persecuted, or unworthy)
• Hallucinations: sensory experiences without external stimuli, most often auditory (hearing voices), but can involve other senses
• Disorganized thinking or speech that reflects the mood-influenced, depressive content
• Severe impairment in judgment or insight during active psychosis)

Not every person with depression and psychotic features will have the same symptoms, and the intensity can fluctuate. The presence of psychotic symptoms typically indicates the need for closer medical supervision, sometimes including hospitalization, to ensure safety and appropriate treatment.

Causes and risk factors

Depression with psychosis arises from a combination of factors that disrupt mood regulation, brain function, and stress coping. The interplay of biology, environment, and personal history helps explain why some people develop this condition.

Biological factors

• Genetic predisposition: a family history of mood disorders or psychotic disorders increases risk.
• Neurochemical changes: imbalances in neurotransmitters such as serotonin, dopamine, and glutamate can influence mood and perception.
• Brain structure and function: alterations in brain circuits involved in emotion, reward, and reality testing may contribute to depressive and psychotic symptoms.

Psychosocial and environmental factors

• Chronic stress, trauma, abuse, or significant life losses
• Social isolation or lack of a support network
• Exposure to discrimination or ongoing stigma related to mental illness

Substance use and medical factors

• Substances such as alcohol, cannabis, or stimulants can worsen mood and precipitate or intensify psychotic symptoms
• Medical conditions (thyroid disorders, autoimmune diseases, infections, neurological illnesses) and certain medications can mimic or aggravate depressive and psychotic symptoms

Risk factors interact in complex ways, and the presence of one or more does not guarantee onset. A clinician considers the full history, current symptoms, and risk signals when evaluating diagnosis and treatment needs.

How professionals diagnose this condition

Diagnosis is based on a comprehensive clinical assessment that combines patient history, symptom patterns, and safety considerations. It typically involves several steps:

• Structured clinical interview and mental status examination to characterize mood, cognition, perception, and behavior
• Assessment for delirium or other medical or neurological causes that could explain symptoms
• Screening for substance use and exposure to toxins
• Use of diagnostic criteria (DSM-5-TR or ICD-11) to determine whether a major depressive episode with psychotic features is present
• Assessment of risk to self or others, including suicide risk, and planning for safety if needed
• Basic medical tests to rule out reversible medical contributors (thyroid function, vitamin levels, metabolic panel, pregnancy tests when relevant)
• May include collateral information from family or close friends and, when appropriate, standardized assessment scales

Imaging or laboratory tests are not used to diagnose depression with psychotic features per se but may help exclude other medical conditions. A careful differential diagnosis helps distinguish psychotic depression from primary psychotic disorders (like schizophrenia), schizoaffective disorder, or bipolar disorder with psychotic features, each of which has its own treatment implications.

Treatment approaches and options

Management typically requires a combination of medication, psychotherapy, and supportive care. The goal is to reduce depressive and psychotic symptoms, address safety concerns, and improve functioning and quality of life. Treatment plans are individualized and may evolve with time.

Medications

• Antidepressants: selective serotonin reuptake inhibitors (SSRIs) such as sertraline or fluoxetine, serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine, or other antidepressants
• Antipsychotics: second-generation (atypical) antipsychotics such as quetiapine, olanzapine, risperidone, or aripiprazole are commonly used as adjuncts to antidepressants to control psychotic symptoms
• Mood stabilizers or anticonvulsants: in some cases, especially if there is bipolar spectrum involvement or mood instability
• Electroconvulsive therapy (ECT): highly effective for severe, treatment-resistant depression with psychotic features or when rapid response is needed (e.g., imminent risk or severe symptoms)

Psychotherapy and behavioral approaches

• Cognitive-behavioral therapy (CBT) for depression, adapted to address psychotic symptoms and provide coping strategies
• Interpersonal psychotherapy (IPT) to strengthen relationships and social functioning
• Family-focused therapy to improve communication, reduce expressed emotion, and support treatment adherence
• Adherence-focused psychoeducation to help patients and families understand the illness and treatment plan

Brain stimulation and other therapies

• Electroconvulsive therapy (ECT): often used when rapid symptom relief is needed or when medications have not worked
• Repetitive transcranial magnetic stimulation (rTMS): a noninvasive option for some patients with depression, sometimes used when antidepressants are not fully effective
• Other supportive interventions: sleep management, exercise programs, nutrition optimization, and stress reduction techniques

Hospitalization and safety planning

• Inpatient care may be necessary if there is high risk of self-harm or harm to others, if medications need close supervision, or if symptoms severely impair daily functioning
• A safety plan, crisis contacts, and clear instructions about when to seek urgent help are essential components of care

Collaborative and ongoing care

Effective treatment often involves coordination among psychiatrists, primary care clinicians, psychologists or therapists, nurses, social workers, and family members or close supporters. Regular follow-up appointments, medication reconciliation, and adjustments based on response and side effects are common parts of long-term care.

Prognosis and living with the condition

The course of depression with psychosis varies widely. Some people respond quickly to treatment, achieve remission, and return to prior levels of functioning. Others may experience recurrent depressive episodes with intermittent psychotic symptoms, requiring long-term treatment strategies and ongoing support. Several factors influence prognosis:

• Early identification and access to comprehensive treatment
• Adherence to a combined treatment plan (medication plus psychotherapy)
• Timely management of safety concerns and suicidality
• Supportive social environment and stable living conditions
• Comorbidity with anxiety, substance use, or other medical conditions

Important evidence-based practices for improving prognosis include sustained pharmacotherapy for an adequate duration, including maintenance treatment after remission if risk of relapse remains high; participation in psychotherapy; lifestyle measures such as sleep regularity, physical activity, and nutrition; and strong social supports. Recovery does not always mean the absence of symptoms, but it often means improved functioning, reduced distress, and a better quality of life.

Support resources

Reliable information and support can make a meaningful difference. If you or someone you know is in immediate danger, call your local emergency number or go to the nearest emergency department. For ongoing support and education, consider these resources:

• National Institute of Mental Health (NIMH) – Depression
• Mayo Clinic – Depression: Symptoms and Causes
• NAMI – Depression
• World Health Organization – Mental Health Fact Sheets

Additional practical supports include local community mental health clinics, patient advocacy organizations, and peer-support groups. Consider asking a trusted clinician or social worker to help connect you with services, housing support, vocational programs, and family education. If you are a caregiver, seek respite care, caregiver training, and counseling to maintain your own wellbeing while supporting a loved one’s recovery.

In the United States, crisis resources include the 988 Suicide & Crisis Lifeline, which provides confidential support 24/7. If you are outside the U.S., seek your country’s equivalent emergency or crisis lines through local health services or international helplines.