uestion: Are psychotic symptoms present?

Show this question in the flowchart.

Help: Any patient with depression in the bipolar spectrum of disorders can have psychotic features such as delusions and hallucinations. The treatment implications seem to be that an antipsychotic will generally be needed as part of the pharmacotherapy regimen. ECT may be used more frequently, but we have already considered that option.

The evidence is strong that psychotic depression in unipolar patients responds best to treatment with a combination of an antipsychotic and an antidepressant.¹ These studies included a small number of bipolar patients, but too few to enable a separate outcome analysis for the bipolars.

¹Osser DN, Patterson RD. Algorithms for the pharmacotherapy of depression: Part One and Part Two. Directions in Psychiatry. 1998;18:303-336. Schatzberg AF, Rothschild AJ. Psychotic (delusional) major depression: should it be included as a distinct syndrome in DSM-IV? Am J Psychiatry. 1992;149:733-745.

Recommendation:

From extrapolation from the literature on unipolar psychotic depression, and from considerable anecdotal experience, it may be assumed that if pharmacotherapy is chosen, an antipsychotic will need to be included in the regimen of patients treated for psychotic bipolar depression. Which antipsychotics would be best to use?

Some older studies have suggested that bipolar patients maintained on typical neuroleptics have an increased risk of cycling into depression,¹ but a more recent study using depot neuroleptics found, on the contrary, that bipolar psychotic depression relapses were prevented by addition of the neuroleptic.² However, a major problem in using typical neuroleptics is the increased vulnerability of bipolar patients to extrapyramidal side effects and tardive dyskinesia.¹ One study (N=131) showed a 35% prevalence of tardive dyskinesia in bipolar patients treated with typical neuroleptics, compared with a total absence of tardive dyskinesia (0% prevalence) in the group treated without them.³ The rate of tardive dyskinesia in vulnerable populations associated with the use of the newer antipsychotics appears to be significantly lower than that with typical neuroleptics.(4)

Therefore, our first-line recommendation in choosing an antipsychotic to treat psychotic bipolar depression is to employ, when possible, one of the newer generation of antipsychotics: olanzapine, quetiapine, and risperidone. (5) There is also consistent evidence that the newer agents have antidepressant activity that is superior to typical neuroleptics in patients with schizophrenia and schizoaffective disorder.(6-8) The data specific to patients with bipolar psychotic depression is very sparse, but two reports with olanzapine involving a total of 18 patients found that 14 had responded well.(9-10) All but two were on an antidepressant also. However, the new antipsychotics may occasionally precipitate agitation or mania (perhaps due to these same antidepressant properties).(11-13) This may necessitate substitution of a different antipsychotic or use of a lower dose. If a parenteral or depot antipsychotic is needed due to patient agitation or non-compliance, a typical neuroleptic must be used, since currently none of the newer generation of antipsychotics is available for parenteral or depot use.

Clozapine is sometimes effective for the treatment-refractory case of bipolar psychotic depression.(14)

To select antidepressants and mood stabilizers to combine with the antipsychotic, continue in the consultation.

Show this question in the flowchart. 

¹Tohen M, Zarate CA, Jr. Antipsychotic agents and bipolar
disorder. J Clin Psychiatry. 1998;59:38-48; discussion 49. ²Littlejohn R,
Leslie F, Cookson J. Depot antipsychotics in the prophylaxis of bipolar
affective disorder. Br J Psychiatry. 1994;165:827-829.
³Mukherjee S, Rosen AM, Caracci G, Shukla S. Persistent tardive
dyskinesia in bipolar patients. Arch Gen Psychiatry. 1986;43:342-346. (4)
Brecher M, Jeste D, Okamoto A, Napolitano J, Kane JM. Low frequency of tardive
dyskinesia in elderly patients with dementia. American College of
Neuropsychopharmcology 37th Annual Meeting. Las Croabas, Puerto Rico; 1998.
(5)	Frye MA, Ketter TA, Altshuler LL, et al. Clozapine in bipolar disorder:
treatment implications for other atypical antipsychotics. J Affect Disord.
1998;48:91-104. (6)	Marder SR, Davis JM, Chouinard G. The effects of risperidone
on the five dimensions of schizophrenia derived by factor analysis:  combined
results of the North American trials. J Clin Psychiatry. 1997;58:538-546.
(7)	Cantillon M, Goldstein JM. Efficacy of quetiapine in affective symptoms of
schizophrenia, NR 445. American Psychiatric Association Annual Meeting. Toronto,
Canada: American Psychiatric Association; 1998. (8)	Tollefson GD, Sanger TM,
Thieme ME. Depressive signs and symptoms in schizophrenia: a prospective blinded
trial of olanzapine and haloperidol. Arch Gen Psychiatry. 1998;55:250-258.
(9)	Rothschild AJ, Bates KS, Boehringer KL, Syed A. Olanzapine response in
psychotic depression. J Clin Psychiatry. 1999;60:116-118. (10)Zarate CA, Jr.,
Narendran R, Tohen M, et al. Clinical predictors of acute response with
olanzapine in psychotic mood disorders. J Clin Psychiatry. 1998;59:24-8.
(11)Lindenmayer JP, Klebanov R. Olanzapine-induced manic-like syndrome [letter].
J Clin Psychiatry. 1998;59:318-9. (12)London JA. Mania associated with
olanzapine [letter]. J Am Acad Child Adolesc Psychiatry. 1998;37:135-6.
(13)Barkin JS, Pais VM, Gaffney MF. Induction of mania by risperidone in
patients resistant to mood stabilizers. J Clin Psychopharmacol. 1997;17:57-58.
(14)Zarate CA, Jr., Tohen M, Baldessarini RJ. Clozapine in severe mood
disorders. J Clin Psychiatry. 1995;56:411-7.