Major depressive disorder with psychotic features

Major Depressive Disorder with Psychotic Features. One severe subtype of depression is characterized by both depressive and psychotic symptoms. Unless a longitudinal history is available, it can be difficult to distinguish a patient with a psychotic depression from a depressed patient who has a comorbid Cluster A personality disorder. Some qualitative features may be helpful, but these are not wholly reliable. The most prominent psychotic symptoms of a psychotic depression tend to be delusions and auditory hallucinations, but these sometimes present in an attenuated form more reminiscent of Cluster A symptoms. 

In eight patients with major depressive disorder without psychotic features, who did not respond to serotonin re-uptake inhibitors therapy when risperidone was added, all improved within 1 week. Furthermore, risperidone also seemed to have beneficial effects on sleep disturbance and sexual dysfunction (47). In an open study in 30 healthy subjects who took risperidone 1 mg orally... 

A 38-year-old man with major depressive disorder and psychotic features developed rabbit syndrome after taking risperidone 4 mg/day and paroxetine 40 mg/ day for 4 months he was also taking simvastatin 10 mg/day, thiamine 100 mg/day, and folic acid 1 mg/ day (104). 

In eight patients with major depressive disorder without psychotic features, who did not respond to serotonin reuptake inhibitors therapy when risperidone was added, all improved within 1 week. Furthermore, risperidone also seemed to have beneficial effects on sleep disturbance and sexual dysfunction (272). In an open study in 30 healthy subjects who took risperidone 1 mg orally before and after venlafaxine dosing to steady state, the oral clearance of risperidone fell by 38% and the volume of distribution by 17%, resulting in a 32% increase in AUC renal clearance of 9-hydroxyrisperidone also fell by 20% (273). The authors concluded that these small effects were consistent with the fact that venlafaxine is unlikely to alter the clearance of risperidone, which is mainly by CYP2D6. 

Schizoaffective and mood disorder exclusion Schizoaffective disorder and mood disorder with psychotic features have been ruled out because either (1) no major depressive, manic, or mixed episodes have occurred concurrently with the active-phase symptoms or (2) if mood episodes have occurred during active-phase symptoms, their total duration has been brief relative to the duration of the active and residual periods. 

Schizophrenia and Schizoaffective Disorder. Cross sectionally, it is often difficult to distinguish major depression with psychotic features from the schizophrenia spectrum disorders. There are theoretically qualitative differences in the psychosis that may help to make the distinction. Psychosis in the context of a mood disorder tends to be manifested by persecutory and nihilistic themes, but schizophrenia is more often characterized by paranoia and disorganization. However,... 

Depressive and anxious symptoms are frequently associated with schizophrenia, but this does not necessarily mean that they fulfill the diagnostic criteria for a comorbid anxiety or affective disorder. Nevertheless, depressed mood, anxious mood, guilt, tension, irritability, and worry frequently accompany schizophrenia. These various symptoms are also prominent features of major depressive disorder, psychotic depression, bipolar disorder, schizoaffective disorder, organic dementias, and childhood... 

Several subtypes of depression require specific treatment strategies that go beyond a simple course of conventional antidepressant therapy (these subtypes include bipolar depression, major depression with psychotic features, seasonal depression, atypical depression, comorbid anxiety disorder, comorbid substance abuse, double depression [major depression... 

It is indicated in the treatment of depressive episodes associated with bipolar disorder. A combination of an antipsychotic drug and an antidepressant may be useful in some cases, especially in depressed psychotic patients, or in cases of agitated major depression with psychotic features. The first combination antipsychotic/antidepressant (olanza-pine/fluoxetine Symbyax) was recently FDA approved in the United States for treatment of depressive episodes associated with bipolar disorder. However, antidepressants and stimulants are unlikely to reduce apathy and withdrawal in schizophrenia, and they may induce clinical worsening in some cases. Adjunctive addition of lithium or an antimanic anticonvulsant, such as carbamazepine, may add benefit in some psychotic patients with prominent affective, aggressive, or resistant symptoms. 

The psychotic disorders include schizophrenia, the manic phase of bipolar (manic-depressive) illness, acute idiopathic psychotic illnesses, and other conditions marked by severe agitation. All exhibit major disturbances in reasoning, often with delusions and hallucinations. Several classes of drugs are effective for symptomatic treatment. Antipsychotic agents also are useful alternatives to electroconvulsive therapy (ECT) in severe depression with psychotic features, and sometimes are used in the management of patients with psychotic disorders associated with delirium or dementia or induced by other agents (e.g., stimulants or L-DOPA). 

Acute mania as part of bipolar I disorder is supposed to result from overexcitation of limbic neurons. This can arise either from loss of inhibitory tonic orbitofrontal control of limbic neurons or from various intra- and intercellular alterations (the full mechanism is unknown as yet). Manic episodes are often classified into euphoric (classical), dysphoric, mixed (along with clinical manifestations of major depressive disorder), mania with psychotic/catatonic features, and mania with a rapid cycling course of the disease. 

Electroconvulsive therapy (ECT) is probably the most effective treatment for major depressive disorder (MDD) with psychotic features, with average response rates of 70-90%, compared with only about 40% for regular antidepressant medications. The response rates for MDD without psychosis are comparable between regular medications and ECT (about 70-75%). ECT is usually given to patients whose condition is refractory to or who are intolerant of antidepressant medication. 

Major depressive disorder (MDD) with psychotic features... 

Given the available data, it is extremely important that clinicians evaluate patients with major depression for features of psychosis, because the failure to do so may result in inadequate treatment for the patient. A practical problem encountered by clinicians, however, is the subtlety of delusions. For example, it is not unusual in geriatric depression for patients to present with a somatic preoccupation that borders on delusional. These so-called near delusions may put the patient into the arena of psychotic depression. Some evidence exists that patients with depression with near delusions may respond more favorably to combinations of antidepressants and antipsychotics or ECT. Once the presence of both major depression and psychosis is determined, other psychotic disorders including bipolar disorder and schizophrenic spectrum illness must also be ruled out because this may influence long-term treatment decisions. 

Bipolar affective (manic-depressive) disorder occurs in 1-3% of the adult population. It may begin in childhood, but most cases are first diagnosed in the third and fourth decades of life. The key symptoms of bipolar disorder in the manic phase are excitement, hyperactivity, impulsivity, disinhibition, aggression, diminished need for sleep, psychotic symptoms in some (but not all) patients, and cognitive impairment. Depression in bipolar patients is phenomenologically similar to that of major depression, with the key features being depressed mood, diurnal variation, sleep disturbance, anxiety, and sometimes, psychotic symptoms. Mixed manic and depressive symptoms are also seen. Patients with bipolar disorder are at high risk for suicide. 

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