Major depressive disorder treatment-resistant

Thus, although few controlled studies have been performed in well-characterized treatment-resistant populations, further studies using these techniques would prove useful in determining the role of these interventions in the treatment of refractory major depressive disorder. 

FIGURE 10—6. Depressive and anxious symptoms are not only a hallmark of major depressive disorder but are frequently associated with other psychiatric disorders, including bipolar disorder, schizophrenia, and schizoaffective disorder with organic causes of depression, such as substance abuse with childhood mood disorders (child) with psychotic forms of depression and with mood and psychotic disorders resistant to treatment with drugs (treatment-resistant), among others. 

Mood symptoms of depression are associated with many conditions in addition to major depressive disorder, including mood and anxiety symptoms in schizophrenia, schizoaffective disorder, bipolar manic/depressed/mixed/rapid cycling states, organic mood disorders, psychotic depression, childhood and adolescent mood disorders, treatment-resistant mood disorders, and many more (see Chapter 10, Fig. 10-6). Atypical antipsychotics are enjoying expanded use for the treatment of symptoms of depression and anxiety in schizophrenia that are troublesome but not severe enough to reach the diagnostic threshold for a major depressive episode or anxiety disorder in these cases the antipsychotics are used not only to reduce such symptoms but hopefully also to reduce suicide rates, which are so high in schizophrenia (Fig. 11 — 53). Atypical antipsychotics may also be useful adjunctive treatments to anti-... 

Papakostas, G. I., Petersen, T. J., Kinrys, G., Bums, A. M., Worthington, J. J., Alpert, J. E., Fava, M. Nierenberg, A. A. (2005). Aripiprazole augmentation of selective serotonin reuptake inhibitors for treatment-resistant major depressive disorder. J. Clin. Psychiatry, 66, 1326-1330. 

Barbee JG, Comad EJ, Jamhour NJ. The effectiveness of olanzapine, risperidone, quetiapine, and ziprasidone as augmentation agents in treatment-resistant major depressive disorder. J Clin Psychiatry 2004 65(7) 975-981. 

The addition of lithium in treating major depressive disorder in patients unresponsive to antidepressant drugs has been discussed, and it has been noted that about 50% of patients respond to lithium augmentation in 2 1 weeks (71), while others have pointed to the absence of controlled data for this treatment in bipolar depression, while nevertheless recommending its use (72). In summary, there are data that support the use of lithium augmentation for treatment-resistant unipolar major depression. However, the data are not robust and are based on only a few hundred patients. Placebo-controlled studies of lithium augmentation for treatment-resistant bipolar depression are lacking (73). 

Well accepted for use in schizophrenia and bipolar disorder, including difficult cases Documented utility in treatment-refractory cases, especially at higher doses Documented efficacy as augmenting agent to SSRIs (especially fluoxetine) in nonpsychotic treatment-resistant major depressive disorder Documented efficacy in bipolar depression, especially in combination with fluoxetine... 

Heresco-Levy, U., Javitt, D.C., Gelfin, Y., Gorelik, E., Bar, M., Blanaru, M., and Kremer, 1. 2006. Controlled trial of d-cycloserine adjuvant therapy for treatment-resistant major depressive disorder. J. Affect. Disord. 93 239-243. 

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

Amsterdam JD, Homig-Rohan M Treatment algorithms in treatment-resistant depression. Psychiatr Clin North Am 19 371-386, 1996 Amsterdam JD, Mozley PD Temporal lobe asymmetry with iofetamine (IMP) SPECT imaging in patients with major depression. J Affect Disord 24 43-53, 1992... 

Psychiatr Chn North Am 19 179-200, 1996 Fava M, Rosenbaum JF, McGrath PJ, et al Dthium and tricyclic augmentation of fluoxetine treatment for resistant major depression a double-blind, controlled study. Am J Psychiatry 151 1372-1374, 1994 Fawcett J Suicide risk factors in depressive disorders and panic disorder. J Clin Psychiatry 53 [suppl 3) 9-13, 1992... 

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. 

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