With Psychotic Features

Psychotic depression has been reported to respond to combined treatment with antidepressants and antipsychotics patients with psychotic depression also show a dramatic response to ECT, which is often the treatment of choice for this disorder. Long-term treatment with antipsychotic medications is generally not warranted, but prophylactic antidepressant medication must be continued as in nonpsychotic depression. 

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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. 

Lithium is effective for acute mania, but it may require 6 to 8 weeks to show antidepressant efficacy. It may be more effective for elated mania and less effective for mania with psychotic features, mixed episodes, rapid cycling, and when alcohol and drug abuse is present. Maintenance therapy is more effective in patients with fewer episodes, good functioning between episodes, and when there is a family history of good response to lithium. It produces a prophylactic response in up to two-thirds of patients and reduces suicide risk by eight- to 10-fold. 

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,... 

Mood Disorder with Psychotic Features. One subtype of major depression and many episodes of mania are associated with psychotic symptoms. Like schizophrenia, the most prominent psychotic symptoms of psychotic depression or mania are delusions and auditory hallucinations. Unless a longitudinal history is available, it is often difficult to distinguish schizophrenia from a psychotic mood disorder. 

When a patient with OCD has impaired insight, the distinction between obsession and delusion becomes blurred. We would argue that such a patient is in fact delusional. The with poor insight specifier is therefore the OCD equivalent to the with psychotic features specifier applied to the mood disorders. There may in fact be a continuum of insight in patients with OCD that fluctuates over time. For example, patients with OCD may recognize that their preoccupation with an obsessional idea or compulsive ritual is excessive, yet they may remain insistent that the premise underlying their anxiety is entirely reasonable. 

Varanka, T.M., Weller, R.A., and Weller, E.B. (1988) Lithium treatment of manic episodes with psychotic features in prepubertal children. Am Psychiatry 145 1557-1559. 

Typical (classical) antipsychotics have been proposed for a wide range of disorders. In the context of EOS the following indications exist acute treatment, maintenance treatment, and relapse prevention of schizophrenic disorders acute treatment and maintenance treatment of schizoaffective disorders treatment of organic mental disorders with psychotic features and... 

Another subgrouping of patients with depression who have a differential pharmacological response are those diagnosed with depression with psychotic features, previously referred to as psychotic depression. These patients generally do not respond well to antidepressant therapy alone but... 

One of the more methodologically rigorous studies on the utility of TCA/antipsychotic combinations in treating PMD was completed by Spiker et al. [1985). In this study, 54 patients who met criteria for depression with psychotic features on the Schedule for Affective Disorders and Schizophrenia [Endicott and Spitzer 1978) and by Research Diagnostic Criteria [Spitzer et al. 1985) were randomly selected to treatment with amitriptyline alone, perphenazine alone, or the combination of two drugs. After a 7-day placebo washout, patients were treated for 35 days with doses averaging approximately 50 mg/day of perphenazine and approximately 200 mg/day of ami-... 

To date, only one study has been completed with an antidepressant other than a TCA combined with an antipsychotic in the treatment of PMD. Rothschild and colleagues (1993) investigated the efficacy of fluoxetine and perphenazine in the treatment of PMD and found that approximately 73% of 30 patients who met DSM-III-R (American Psychiatric Association 1987) criteria for major depression with psychotic features had at least a 50% reduction on their Hamilton Rating Scale for Depression scores over 5 weeks. Furthermore, the combination of fluoxetine and perphenazine appeared to be better tolerated than the combination of TCAs with antipsychotics. Although there is no evidence that monotherapy with an antidepressant other than amoxapine is efficacious, the combination therapy with many antidepressants other than the TCAs may prove useful. 

Depression with psychotic features Antidepressant+antipsychotic, or ECT avoid bupropion... 

Because the most common condition studied is schizophrenia, this is the primary disorder discussed. We also consider schizophrenic spectrum (e.g., delusional, schizophreniform, schizoaffective) mood disorders with psychotic features and various nonpsychotic conditions (e.g., in the developmentally disabled) for which antipsychotics have been used (see Appendix A Appendix C Appendix E, Appendix F. and Appendix G). 

Because it can be difficult to distinguish a severe, apathetic depression from a patient with catatonic features, an augmenting antidepressant should be considered. These agents may also help a post-psychotic depression, suggesting the importance of identifying subgroups that might benefit from this approach. This combination is also much more effective than antidepressant monotherapy in depression with psychotic features (see also Chapter 6 and Chapter 7). 

Lithium or alternate treatments, such as valproate or carbamazepine, for bipolar, manic schizoaffective and schizophreniform disorders (alternate nonneuroleptic interventions may be better in light of reports that affectively disordered patients with psychotic features may be more susceptible to TD and NMS). 

A retrospective study of 52 delusionally depressed patients suggested that there may be various subgroups bipolar, early onset unipolar and possibly unipolar, late onset (12). As with previous reports, there was a remarkably high rate of psychotic relapse in those patients who manifested psychotic symptoms at the index admission (i.e., depression or mania with psychotic features). Moreover, psychotic features were more common in bipolar than in unipolar depression. 

Lithium Plus Antipsychotics. Many patients present in a very explosive, belligerent, and agitated manner, and waiting several days to weeks to gain control of an episode is not feasible. Thus, antipsychotics alone or as adjuncts are frequently required in the earliest phases of treatment, particularly with moderate to severe exacerbations, often associated with psychotic features. As a result, antipsychotics are the most commonly used adjunctive agents, because more than half of all acutely ill bipolar patients present with psychotic symptoms. In addition, many require maintenance antipsychotics to prevent frequent relapses. Antipsychotics are usually initiated in conjunction with lithium because of their more rapid impact, then carefully tapered and discontinued, when possible, after the full effect of lithium is realized. 

McElroy and her coworkers (109) surveyed the response of 85 consecutive patients, including 14 bipolar patients with psychotic features, who received clozapine for 6 weeks. The response rates of the schizoaffective patients (both bipolar and depressed subtypes), as well as those with bipolar disorders with psychotic features, were excellent (i.e., almost 90%) and substantially better than the response rate for the pure schizophrenic group (i.e., 46%). 

Lyketsos and colleagues (485) have reported a dramatic, sustained increase in depressive symptoms as early as 18 months before the clinical diagnosis of AIDS. Mood disturbance, primarily depression, can range from mild adjustment phenomena to a major depressive episode with psychotic features. Depression in this group can be categorized as... 

For approximately 70% of patients with schizophrenia, and probably for a similar proportion of patients with bipolar disorder with psychotic features, typical and atypical antipsychotic drugs are of equal efficacy for treating positive symptoms. However, the evidence favors atypical drugs for benefit for negative symptoms and cognition, for diminished risk of tardivedyskinesia and other forms of EPS, and for lesser increases in prolactin levels. 

Many of the genes that increase vulnerability to bipolar disorder are common to schizophrenia but some genes appear to be unique to each disorder. Genome-wide association studies of psychotic bipolar disorder have shown replicated linkage to chromosomes 8p and 13q. Several candidate genes have shown association with bipolar disorder with psychotic features and with schizophrenia. These include genes for dysbindin, DAOA/G30, disrupted-in-schizophrenia-1 (DISC-1), and neuregulin 1. 

Mania, depression, and cognitive disorders like Alzheimer s disease may or may not be associated with psychotic features. True or False. 

Paxil is probably especially punishing in regard to causing both acute adverse effects and withdrawal. In a double-blind study, Zanardi et al. (1996) administered Zoloft and Paxil to inpatients diagnosed with depression with psychotic features. Within 2 weeks of starting treatment, 41% of the Paxil patients dropped out because of unpleasant side effects... 

Neuroleptic drugs are often used in mood stabilizer combinations. However, there have been few controlled studies of the use of such combinations, and interactions are potentially dangerous. The advantages and disadvantages of all currently used mood stabilizer combinations have been extensively reviewed (641). Some effects are well known neurotoxicity, hypotension, somnambulistic-like events, and cardiac and respiratory arrest associated with the combination of lithium and traditional neuroleptic drugs considered as a first-line treatment for classic euphoric mania with psychotic features. 

The combination of valproate and traditional neuroleptic drugs, a first-line treatment for mixed or rapid-cycling episodes or dysphoric mania with psychotic features, is associated with altered mental status and electroencepha-lographic abnormalities (641). 

The aim of another study was to evaluate the long-term efficacy of clozapine in patients with treatment-resistant schizophrenia (n = 34), schizoaffective disorder, bipolar type (n = 30), or bipolar disorder with psychotic features (n = 37), who were treated with clozapine in flexible doses over 48 months (16). After this time, Global Assessment of Functioning scores were improved in all three groups, with significantly greater improvement in the bipolar disorder group compared with the others ... 

A combination of olanzapine and fluoxetine was used in two randomized, double-blind simultaneous 8-week trials in 249 patients with major depression with psychotic features (trial 1 n = 124, mean age 41 years, 52% women trial 2 n = 125, mean age, 41 years, 50% women), which have been jointly published (69). This multicenter study was completed by 51 subjects in trial 1 (41%) and 59 subjects in trial 2 (47%). Altogether, there were no significant differences in the rates of discontinuation due to adverse events among the different treatment groups placebo (n = 100), monotherapy with olanzapine 5-20 mg/day (n = 101), and olanzapine 5-20 mg/day plus fluoxetine 20-80 mg/day (n = 48). Dropout percentages were 59% in trial 1 (similarly distributed in the three groups) and 53% in trial 2 (ranging from 40% of dropouts... 

Rothschild AJ, Williamson DJ, Tohen MF, Schatzberg A, Andersen SW, Van Campen LE, Sanger TM, Tollefson GD. A double-blind, randomized study of olanzapine and olanzapine/fluoxetine combination for major depression with psychotic features. J Clin Psychopharmacol 2004 19 365-73. 

A patient taking diltiazem developed the signs and symptoms of mania (114) and another developed mania with psychotic features (115). There have also been reports that nifedipine can cause agitation, tremor, belligerence, and depression (116), and that verapamil can cause toxic delirium (117). Nightmares and visual hallucinations have been associated with nifedipine (118). Depression has been reported as a possible adverse effect of nifedipine (119). 

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