Lynsey Tamborello, MD Suboxone Treatment

Dr Tamborello's Psychiatry Blog.

Lynsey P. Tamborello, MD, et al, Psychopharmacological Treatment for Palliative Care Patients, Psychiatric Annals (2012)42:142-146

Abstract: With America's expanding aging population; the recent greater emphasis on patient autonomy; and ongoing advancements in chemotherapy, oncologists, internists, and palliative care specialists are turning to psychiatrists more often for the management of psychological and behavioral problems. Half of all patients with terminal illness meet DSM-IV criteria for a psychiatric disorder such as adjustment disorder, major depression, anxiety disorders, or delirium.

Additionally, psychiatrists assist palliative care patients in dealing with somatic complaints such as pain, insomnia, shortness of breath, and nausea, all of which may be exacerbated by psychiatric conditions.

In this article, we review the efficacy and safety of the treatments most commonly used by psychiatrists in palliative care settings.

Machado-Vieira R, Soares JC, Lara DR, Luckenbaugh DA, Busnello JV, Marca G, Cunha A, Souza DO, Zarate CA Jr, Kapczinski F., A double-blind, randomized, placebo-controlled 4-week study on the efficacy and safety of the purinergic agents allopurinol and dipyridamole adjunctive to lithium in acute bipolar mania., J Clin Psychiatry. 2008 Aug;69(8):1237-45.

OBJECTIVE: The therapeutics for bipolar disorders are still far from adequate, and new options with improved effectiveness, safety, and tolerability in a wide range of patients are necessary. Preliminary data have suggested a role for dysfunctions targeting the purinergic system in mood disorders. This study aimed to evaluate the efficacy and tolerability of the purinergic agents allopurinol and dipyridamole combined with lithium in bipolar mania. METHOD: A randomized, placebo-controlled, double-blind study was performed in adult inpatients (N = 180) with a DSM-IV-TR diagnosis of bipolar I disorder, current episode manic with or without psychotic features (rapid cyclers and mixed episodes were not included). No antipsychotic agent was used during the study. Subjects were given fixed oral doses of either allopurinol 600 mg/day (N = 60), dipyridamole 200 mg/day (N = 60), or placebo (N = 60) added to lithium for 4 weeks. Subjects were rated at baseline and days 7, 14, 21, and 28 using the Young Mania Rating Scale (YMRS) as the primary efficacy measure. The study was conducted between September 2003 and September 2006. RESULTS: Allopurinol resulted in greater mean reductions in YMRS scores from baseline to day 21 (p < .001) and day 28 (p = .003) compared with placebo using a linear model analysis (d = 0.32, 95% CI = 0.07 to 0.57). Remission rates were significantly higher for allopurinol compared with dipyridamole and placebo (p = .008). Lithium showed a significant antimanic efficacy even in the placebo group. Decrease in plasma uric acid levels showed a significant positive association with antimanic effects in the allopurinol group (p < .001). CONCLUSION: Allopurinol is clinically effective and well-tolerated adjunctively with lithium in manic episodes and may represent an alternative approach in the treatment of acute mania, especially for those presenting tolerability and safety issues with antipsychotics. The present results strongly support the involvement of the purinergic system in the pathophysiology and therapeutics of bipolar disorder. Further placebo-controlled studies with allo-purinol compared with standard mood stabilizers in mania and maintenance are warranted.

Ronald S. Duman, George K. Aghajanian, Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science (2012) Vol. 338 no. 6103 pp. 68-72 DOI: 10.1126/science.1222939


Basic and clinical studies demonstrate that depression is associated with reduced size of brain regions that regulate mood and cognition, including the prefrontal cortex and the hippocampus, and decreased neuronal synapses in these areas. Antidepressants can block or reverse these neuronal deficits, although typical antidepressants have limited efficacy and delayed response times of weeks to months. A notable recent discovery shows that ketamine, a N-methyl-d-aspartate receptor antagonist, produces rapid (within hours) antidepressant responses in patients who are resistant to typical antidepressants. Basic studies show that ketamine rapidly induces synaptogenesis and reverses the synaptic deficits caused by chronic stress. These findings highlight the central importance of homeostatic control of mood circuit connections and form the basis of a synaptogenic hypothesis of depression and treatment response.

Modified for psychiatry blog use

Yao JK, et al, Associations between Purine Metabolites and Clinical Symptoms in Schizophrenia. PLoS One. 2012;7(8):e42165..

BACKGROUND: The antioxidant defense system, which is known to be dysregulated in schizophrenia, is closely linked to the dynamics of purine pathway. Thus, alterations in the homeostatic balance in the purine pathway may be involved in the pathophysiology of schizophrenia.

METHODOLOGY/PRINCIPAL FINDINGS: Breakdown products in purine pathway were measured using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system for 25 first-episode neuroleptic-naive patients with schizophrenia at baseline and at 4-weeks following initiation of treatment with antipsychotic medication. Associations between these metabolites and clinical and neurological symptoms were examined at both time points. The ratio of uric acid and guanine measured at baseline predicted clinical improvement following four weeks of treatment with antipsychotic medication. Baseline levels of purine metabolites also predicted clinical and neurological symptoms recorded at baseline; level of guanosine was associated with degree of clinical thought disturbance, and the ratio of xanthosine to guanosine at baseline predicted degree of impairment in the repetition and sequencing of actions.

CONCLUSIONS/SIGNIFICANCE: Findings suggest an association between optimal levels of purine byproducts and dynamics in clinical symptoms and adjustment, as well as in the integrity of sensory and motor processing. Taken together, alterations in purine catabolism may have clinical relevance in schizophrenia pathology.<>

Chiu CC, et al, The relationship between serum uric acid concentration and metabolic syndrome in patients with schizophrenia or schizoaffective disorder. Clin Psychopharmacol. 2012 Oct;32(5):585-92,

ABSTRACT: Higher prevalence rates of metabolic syndrome (MetS) in patients with schizophrenia are getting more and more attention. Uric acid (UA) has been frequently reported to be associated with MetS in the general population. Sex difference in this relationship is inconsistent. As a selective antioxidant, UA has also been found to be reduced in patients with schizophrenia, and this effect may be prominent in men. With the inconsistent presentations, higher rate of MetS but possible lower UA concentrations, the aim of this study was to investigate the r elationship by sexes between serum UA concentrations and prevalence of MetS in patients with schizophrenia or schizoaffective disorder. A total of 637 patients, 342 male and 295 female, were enrolled from 36 psychiatric rehabilitation institutions. Cross-sectional anthropometrical data, biochemical analysis, and serum UA were measured. Serum UA concentrations were divided into quartiles by sexes. Modified National Cholesterol Education Program Adult Treatment Panel III criteria for Asians were used as diagnosis of metabolic syndrome. After adjustment, higher uric acid concentrations are associated with hypertriglyceridemia, low high-density lipoprotein cholesterol level, and high blood pressure in men and with hypertriglyceridemia in women. Significantly higher odds ratios for metabolic syndrome in the UA third compared with the lowest quartile were found in men but not in women after adjustment. These results suggest that lower UA concentrations in male patients with schizophrenia or schizoaffective disorder are associated with lower risk of MetS.


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