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I just want to know how, if they do work as such, given the strong dopamine release...it just seems counter-intuitive
N&PD Moderators: Skorpio | thegreenhand
Med Sci Monit. 2012 Jul;18(7):HY23-6.
Low dose morphine adjuvant therapy for enhanced efficacy of antipsychotic drug action: potential involvement of endogenous morphine in the pathophysiology of schizophrenia.
Stefano GB, Králíčková M, Ptacek R, Kuzelova H, Esch T, Kream RM.
Source
Neuroscience Research Institute, State University of New York-College at Old Westbury, Old Westbury, NY 11568, USA. [email protected]
Abstract
Major thematic threads linking extensive preclinical and clinical efforts have established a working mechanistic scheme whereby atypical antipsychotic drugs ameliorate negative DSM IV diagnostic criteria by effecting relatively potent blockade of serotonin (5-HT)(2A) receptors coupled with weaker antagonism of dopamine D(2) receptors in frontal cortical areas. These contentions are more or less supported by in vitro binding experiments employing cloned receptors on cultured cells, although significant functional involvement of 5-HT(2C) receptors has also been proposed. It is interesting that a key statistical analysis indicates a major shift in usage back to typical antipsychotic agents for management of schizophrenia from 1995-2008, whereas off-label usage of atypical antipsychotic agents was markedly increased or expanded for bipolar affective disorder. Importantly, meta-analyses generally did not support efficacy differences between the other atypical antipsychotics compared with the older typical agents. A critical examination of putative functional linkages of morphine and its type-selective mu opioid receptor to higher order cortical regulation of cognitive processes may provide novel insights into human behavioral processes that are severely impaired in schizophrenia spectrum disorders.
PMID: 22739740 [PubMed - indexed for MEDLINE]
Heroin Add & Rel Clin Probl 1999; 1 (1): 43-44 Letters to the Editor
Methadone as a Mood Stabilizer
Pier Paolo Pani, Alessandro Agus, Gian Luigi Gessa
TO THE EDITOR: The positive effect of opioid agonists in psychotic disorders has
repeatedly been hypothesized. Methadone has been noted as interfering positively with
depressive affects and psychotic rage (3); buprenorphine has been considered for its
antidepressant activity (2).
We report a case in which methadone seems to have a role in the treatment of a
bipolar mood disorder.
Mr. A was admitted to a methadone maintenance treatment program (MMTP) at age
26, after three years of heroin addiction. Upon intake he exhibited major depression
(according with DSM-III-R), with anxiety, guilt and suicidal thinking, which subsided
within 10 days of treatment with methadone (50 mg/day). The MMTP, lasting three
years, was interrupted because of six months’ incarceration for old crimes. Mr. A was
readmitted to a MMTP two months after release, relating his heroin-relapse to a new
depressive episode begun while in prison. Major depression was again ascertained,
subsiding only with methadone treatment (40 mg/day).
After four years of heroin-free MMTP (morphinuria-results confirmed), Mr. A
requested detoxification, as he had the chance to commute impending imprisonment for
a therapeutic community programme. After a complete medical and psychiatric
evaluation, detoxification was started and accomplished within 7 days of in-patient
treatment with clonidine and benzodiazepines. At discharge, the patient started feeling
extraordinarily well, attractive and successful. This status evolved rapidly into mania
(according to DSM-IV), with euphoria, insomnia, delusions and hallucinations. Over
the next two months the patient was repeatedly hospitalized and treated with neuroleptics
and benzodiazepines. While euphoria, delusions and hallucinations subsided, restlessness,
nervousness and insomnia increased. There were rapid mood shifts from dysphoria to
depression, and suicidal thoughts appeared. Mr. A started stating that only methadone
could give him relief. A mixed status was diagnosed (according to DSM-IV), and
treatment started with lithium and carbamazepine (serum concentration were 0.70 mEq/
L and 9.5 µg/mL, respectively), as well as clonazepam and clotiapine ( 6 and 80 mg/day,
respectively). After one month without improvement, Mr. A came to the service,
2
“Bernard B. Brodie” Department of Neuroscience, University of Cagliari, Italy
1
SerT, AUSL 8, Cagliari, Italy44
Heroin Addiction and Related Clinical Problems
claiming heroin use in the preceding three days in order to be allowed to re-enter the
MMTP. After toxicological urinalysis confirmation, he was re-accepted into the
programme and medicated with methadone (30 mg/day). In a few days his mood
improved, and anxiety, insomnia and dysphoria subsided. This improvement continued
with the increase of the daily dose to 50 mg. Upon follow-up, two months later, his mood
was stable and the urine samples were consistently morphine-free. The patient was still
taking methadone (50 mg/day), clotiapine (40 mg/day), lithium and carbamazepine
(serum concentrations were 0.65 mEq/L and 9.4 µg/mL, respectively).
The improvement of depression and psychotic symptoms in patients on methadone
has been previously reported (3), as has the existence of psychosis during methadone
detoxification (1); thus methadone appears to share some characteristics of mood
stabilizers like lithium or carbamazepine.
Our case seems to confirm the mood-stabilizing effect of methadone. Our patient
spent a total of seven years in methadone maintenance and only one year out of it, both
polarities of mood disorder being concentrated within this short period of time and
resolved rapidly on re-entering the MMTP. Thus methadone may have played some role
in preventing mood disorder relapses.
References
1. Bodkin J.A., Zornberg G.L., Scott E.L., Cole J.O. (1995): Buprenorphine
treatment of refractory depression. J Clin Psychopharmacol. 15 (1): 49-56.
2. Levinson I., Rosenthal R. N. (1995): Methadone withdrawal psychosis. J Clin
Psychiatry 56 (2): 73-76.
3. McKenna G.J. (1982): Methadone and opiate drugs: Psychotropic effect and selfmedication. In Verebey K. Ed. Opioids in mental illness: theories, clinical
observations, and treatment possibilities. The New York Academy of Science,
New York.
Received and Accepted January, 15, 1999
I just want to know how, if they do work as such, given the strong dopamine release...it just seems counter-intuitive
what other drugs increase prolactin?
In one of the studies using methadone IIRC the increase in prolactin was directly correlated with antipsychotic effects.
Seventy-three malignant tumors were identified in the hyperprolactinemia patients and 660 tumors in the comparison group (HR 1.31; 95% confidence interval (CI): 1.02-1.68), mainly attributed to an increased risk of upper gastrointestinal cancer in both males and females (HR 3.69; 95% CI: 1.70-8.03) and hematopoietic cancer in females (HR 3.51; 95% CI: 1.06-11.6). Twelve breast cancers occurred in the female patients, corresponding to an HR of 1.09 (95% CI: 0.60-1.99). Prostate cancer risk in hyperprolactinemia men was reduced (HR 0.40; 95% CI: 0.16-0.99).
Opiates increase prolactin. antipsychotics increase prolactin. Prolactin inhibits dopamine, and prolactin increase is a common effect of nearly 100% (maybe not abilify) of antipsychotics and contributes to the antipsychotic effect.