Does the antidepressive response to
opiate treatment describe a subtype of depression

Nyhuis-P-W, Specka-M, Gastpar-M
European Neuropsychopharmacology, 2006, Vol 16, Supp 4, S309


Background: Though opium and its derivates is still used in medical therapy today only as a strong analgesic, the history of this group of substances is shaped much from their use of mental disorders, which can be traced back into Europe's Psychiatry of the Classic Era (1). First the development of the MAO-inhibitors and he tricyclic antidepressants detached the administration of opiates as the most conventional medicinal treatment form of depressive disorders. in the last decades, only a few publications reported on the antidepressive effects of opiates (2), in particular of buprenorphine, which was attributed an especially small potential for development of dependence, on account of its mixed partially agonistic activity on the u-opioid-receptor and antagonists activity on the e-opioid receptor. Moreover, buprenorphine shows a favourable influence on affectivity, as is known from the substitution treatment of heroine addicts and also in non-addicted patients. But it is still not clear, which depressed patients benefit from a treatment with opiates and which don't. Nowadays, despite the expanding armary of the newer antidepressants, about 23-30% of patients do not respond to medication and 12-15% of these lead to a chronic depression. Though the dexamethasone suppression test (DST) has a sensitivity of only 40-70% in severe depression, it is one of the few neuroendocrine strategies that offers insights in the pathophysiology of depression and will help define more homogeneous subgroups from a bioclinical and therapeutic viewpoint. Method: In an open label study we included 11 patients (7 f, 4m, 51.2y) suffering from severe depression according to the ICD-10-criteria for at least 12 months. The patients were refractory to SSRI's tricyclic antidepressants, tranylcypromine, venlafaxine and various combinations. the DST followed after a wash-out-phase of 3 days without any antidepresants (2mg dexamethasone at 11 pm, serum cortisol level at 8 am). Then the patients were administered buprenorphine as monotherapy in a final dosage of 0.8-2.0 mg once daily. the course was documented with the HAMD and the BDI.

Results: Within 1 week, 7 patients responded to buprenorphine corresponding to a decrease in the HAMD and the BDI scores for at least 50%. In 5 responders, the cortisol levels were completely suppressed, 2 responders achieved cortisol levels of 1.3 and1.6ug/dl. The 4 non-responders achieved cortisol levels of1.0, 2.0, 2.1 (p=0.02).

Conclusion: The DST in depressed patients responding to buprenorphine yielded significantly lower cortisol levels than in non-responding patients. However, cortisol secretion and failure to suppress cortisol in response to dexamethasone have been consistently associated with severe depression (3). Possibly, the response to opiates describes a special subtype of depressive disorders e.g corresponding to a dysregulation of the endogenous opioid system and not of the monaminergic system.

Opiates as antidepressants
Antidepressants: methadone?
Is morphine an antidepressant?
Depression, opioids and the HPA
Endomorphins as antidepressants?
Opiates for treatment-resistant depression
Opioids, depression and learned helplessness
Use of oxycodone and oxymorphone to treat major depression

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