Psychotic depression treatment

Mood stabilizers or atypical antipsychotics tor bipolar depression, psychotic depression, treatment-resistant depression, or treatment-resistant anxiety disorders... 

Electroconvulsive therapy (ECT) is the application of prescribed electrical impulses to the brain for the treatment of severe depression, mixed states, psychotic depression, and treatment-refractory mania in patients who are at high risk of suicide. It also may be used in pregnant women who cannot take carbamazepine, lithium, or divalproex. 

Compared to antipsychotics, there are even fewer studies on the prescribing patterns of antidepressants done in Asian countries. Pi etal. (1985) conducted a survey of psychotropic prescribing practices reported by psychiatrists in 29 medical schools in 9 Asian countries. Daily dose range of tricyclic antidepressants (TCAs) such as amitriptyline, imipramine, and nortriptyline in Asian countries was comparable to the practice in USA. This is despite differences found between Asian and non-Asian populations in the pharmacokinetics of TCAs (Pi et al, 1993). A questionnaire on the practical prescribing approaches in mood disorders administered to 298 Japanese psychiatrists was reported by Oshima et al. (1999). As first-line treatment, the majority of respondents chose newer TCAs or non-TCAs for moderate depression and older TCAs for severe depression. Combination of antidepressants and anxiolytics was preferred in moderate depression, while an antidepressant and antipsychotic combination was common in severe psychotic depression. Surprisingly, sulpiride was the most favored drug for dysthymia. In a naturalistic, prospective follow-up of 95 patients with major depression in Japan, the proportion of patients receiving 125 mg/day or less of imipramine was 69% at one month and 67% at six months (Furukawa et al., 2000). 

Most treatment-resistant depressed patients have received inadequate therapy. Issues to be considered in patients who have not responded to treatment include the following (1) Is the diagnosis correct (2) Does the patient have a psychotic depression (3) Has the patient received an adequate dose and duration of treatment (4) Do adverse effects preclude adequate dosing (5) Has the patient been compliant with the prescribed regimen (6) Was treatment outcome measured adequately (7) Is there a coexisting or preexisting medical or psychiatric disorder (8) Was a stepwise approach to treatment used (9) Are there other factors that interfere with treatment ... 

For the treatment of psychoneurotic patients with depression or anxiety depression or anxiety associated with alcoholism or organic disease psychotic depressive disorders with associated anxiety including involutional depression and manic-depressive disorders. 

Antidepressant drugs, such as the tricyclic antidepressants and the selective serotonin reuptake inhibitors (SSRIs), are very important for the treatment of psychotic depression (see Chapter 34). They have been shown to be effective when used in the treatment of several anxiety disorders, including general anxiety, obsessive-compulsive disorder, and several phobias, including agoraphobia. Because the SSRIs are less toxic than the tricyclic antidepressants, their use in the treatment of anxiety is safer and less likely to produce serious side effects. 

Mania. Mania and hypomania can also occur in children and adolescents on SSRIs, and, again, it is not known if there is an added developmental risk (Ven-kataraman et al., 1992). In a fluoxetine treatment study for depression, 3 (of 48) patients developed manic symptoms, even after excluding patients with psychotic depression, bipolar symptoms, or a family history of bipolar disorder (Emslie et al., 1997). In a paroxetine treatment study for depression, 5 adolescents (of 93) were removed for emotional lability and 1 for eupho-ria/expansive mood (Keller et al., 2001). 

The primary indication for ECT in adolescents is the short-term treatment of mood symptoms, depressive or manic (Walter et al., 1999). Mood symptoms in the course of major depression, psychotic depression, bipolar disorder, organic mood disorders, schizophrenia, and schizoaffective disorder respond well to ECT. Psychotic symptoms in mood disorders also respond well to ECT whereas the effectiveness of ECT in the treatment of psychotic symptoms in schizophrenia is doubtful. There are suggestions that other uncommon clinical conditions in adolescents such as catatonia and neuroleptic malignant syndrome also benefit from ECT. The effectiveness of ECT seems to lessen when there is a comorbid personality disorder or drug and/or alcohol problems. There are very few data about usefulness on prepubertal children. 

Substantial evidence supports the theory that psychotic depression represents a distinct type of major depression (Schatzberg and Rothschild 1992). Statistically significant differences between psychotic and nonpsychotic major depression have been noted along many axes, including presenting features (Coryell et al. 1984 Frances et al. 1981 Classman and Roose 1981 Lykouras et al. 1986 J. C. Nelson and Bowers 1978), biology (Carroll et al. 1976a Coryell et al. 1982 Rihmer et al. 1984 Rudorfer et al. 1982), familial transmission (Leckman et al. 1984 W. H. Nelson et al. 1984), course of illness (D. G. Robinson and Spiker 1985), and response to treatment (Chan et al. 1987 Classman and Roose 1981 Kantor and Classman 1977 J. C. Nelson and Bowers 1978 Rothschild 1985). 

To date, only one antidepressant, amoxapine, has proven effective in the treatment of PMD as the sole therapy. Amoxapine is a chemical congener of the antipsychotic drug loxapine, so it possesses both dopamine-blocking and monoamine-enhancing properties. One double-blind study has confirmed that amoxapine appears to be as effective as the combination of a TCA and an antipsychotic. R. F. Anton and Burch [1990] randomly selected 46 inpatients with psychotic depression to either amoxapine [to 400 mg/day] or ami-... 

Several conclusions can be drawn from the current literature on the treatment of psychotic depression ... 

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. 

TCAs in more serious forms of depression such as melancholic or psychotic depression. Some studies have suggested that the SSRls do not work as well as the TCAs in melancholic depression (Roose et al. 1994]. Likewise, one study has suggested that venlafaxine, a drug with a mechanism of action similar to that of the TCAs, was superior to fluoxetine in the treatment of inpatients with melancholic depression (Clerc et al. 1994]. Still, other metaanalyses have failed to find a difference in the efficacy of SSRls versus TCAs in serious forms of depression [Nierenberg 1994]. Nonetheless, given that most studies have employed TCAs, and some debate exists about the utility of SSRls in severe subtypes, it may be prudent to start with a TCA in most patients until the debate is further resolved. For patients who present a significant suicide risk or who have not been able to tolerate TCAs, the SSRls in combination with a standard antipsychotic appears an effective option. 

The available data indicate that patients with PMD will often respond to combination drug therapy or amoxapine at adequate doses (>200 mg/day for amoxapine or TCAs] for at least 4 weeks. However, the course of psychotic depression is often prolonged, and it may take several months of treatment before a remission is secured. 

Anton RF Jr, Burch EA Jr A comparison study of amoxapine versus amitiiptyhne plus perphenazine in the treatment of psychotic depression. Am J Psychiatry 147 1203-1208, 1990... 

Anton RF Jr, Burch EA Jr Response of psychotic depression subtypes to pharmacotherapy. J Affect Disord 28 125-131, 1993 Anton SF, Robinson DS, Roberts DL, et al Long-term treatment of depression with nefazadone. Psychopharmacol Bull 30 165-169, 1994 Aoba A, Kakita Y, Yamaguchi N, et al Absence of age effect on plasma halopeiidol neuroleptic levels in psychiatric patients. J Gerontol 40 303-308, 1985 Appel SC Treatment of Alzheimer disease, in Chnical Imphcations of Neurotrophic Factors. Edited by Appel SC. Philadelphia, PA, Dppincot-Raven, 1997, pp 156-175... 

Kocsis JH, Croughan JL, Katz MM, et al Response to treatment with antidepressants of patients with severe or moderate nonpsychotic depression and of patients with psychotic depression. Am J Psychiatry 147 621-4, 1990... 

Nelson JC, Mazure CM Lithium augmentation in psychotic depression refractory to combined drug treatment. Am J Psychiatry 143 363-366, 1986... 

Rothschild AJ Delusional depression a review of the literature and current perspectives. McLean Hospital Journal 2 68-83, 1985 Rothschild AJ, Samson JA, Bessette MP, et al Efficacy of the combination of fluoxetine and perphenazine in the treatment of psychotic depression. J Clin Psychiatry 54 338-342, 1993... 

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. 

As Weissman et al. (1987) emphasized in a review some years ago, the utility of several psychotherapeutic procedures in the treatment of unipolar non-psychotic depressions has been shown convincingly in a number of independent, controlled studies. Clearly structured procedures with time limits, such as CT. IPT and SST, represent valuable alternatives or a supplement to drug therapy with antidepressants, especially in outpatients. This view is supported by the large, carefully controlled study by Keller et al. (2000, see above), which resulted in very similar response rates for drug treatment and... 

Clarify atypical or specific subtypes of presentations that may not benefit from standard treatments (e.g., atypical or psychotic depressive disorders). 

Failure to identify the specific subtype may delay the most effective treatment, particularly with psychotic depression. 

Treatment Implications. A review of response rates found that only 35% of patients with psychotic depression responded to treatment with a tricyclic antidepressant alone versus 67% of patients with nonpsychotic depression (Table 6-6) (13). Yet these patients have a better response to electroconvulsive therapy (ECT) (14). These patients have also been found to respond to combined treatment with an antidepresssant and an antipsychotic in comparison with either an antidepressant or antipsychotic alone (15). Despite these data, one study found that less than 50% of patients with psychotic depression referred to an ECT service had been treated with an antipsychotic and only 15% had received a daily dose equivalent to 200 mg or more or chlorpromazine ( 16). 

At one time, TCAs were thought to be more effective than the MAOIs, but recent investigation has found these two classes equally effective ( 184). The poorer showing in some of the earlier studies was the result of subtherapeutic doses of MAOIs administered to treatment-resistant populations (e.g., psychotic depressions, which are... 

Lithium Lithium augmentation of standard antidepressants has been reported to significantly benefit previously treatment-resistant and psychotic depressions, particularly in bipolar patients ( 371, 372). There is substantial case report literature reporting that many patients have benefited when lithium was added to ongoing TCA therapy. Often these results occurred rapidly, sometimes with low doses of lithium. Although the results of controlled trials have not been as dramatic, they still support this approach, which should be seriously considered for treatment-resistant major depression. 

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