Taking vitamin D with quetiapine can help avoid new-onset diabetes risk

In continuation of my update on quetiapine

Atypical antipsychotics, though effective for treating disorders like schizophrenia, bipolar disorder, and depression, gives patients a heightened risk of developing new-onset diabetes. A new data mining study, however, has found a way to relieve this side effect. The study, published in Scientific Reports, shows that taking vitamin D ameliorates the risk of developing new-onset diabetes from atypical antipsychotics like quetiapine.

 quetiapine.

The consequences of developing diabetes from taking antipsychotics are dire, as they occasionally cause life-threatening conditions and sometimes even death.

Members of Shuji Kaneko's lab at Kyoto University looked for potential antidotes on the US FDA's Adverse Event Reporting (FAERS) system, which is the largest database of self-reported adverse side effects. "We found that patients who had coincidentally been prescribed vitamin D with quetiapine were less likely to have hyperglycaemia," says Kaneko. "It's unusual for vitamin D to be prescribed with quetiapine because it is typically prescribed to treat osteoporosis; in fact, there were only 1232 cases in the world where vitamin D was prescribed with quetiapine. Data mining proved helpful in locating these cases."

The team confirmed this finding with further tests on mice; the group of mice that was fed vitamin D along with quetiapine had significantly lower levels of blood sugar than those that took only quetiapine.

"Interestingly, vitamin D on its own doesn't lower diabetes risk, but it certainly defends against the insulin-lowering effects of quetiapine," elaborates lead author Takuya Nagashima. "We clarified the molecular mechanisms of how quetiapine causes hyperglycaemia using datasets in a genomics data repository. Through this we found that quetiapine reduces the amount of a key enzyme called PI3K that gets produced. Vitamin D stops quetiapine from lowering PI3K production."

"Databases like FAERS aren't just for making drug regulations; they have so much potential for side-effect relief using pre-existing drugs," says Kaneko. "There's a lot we can hope for from reverse translational research like this. "

Ref : http://www.kyoto-u.ac.jp/en/research/research_results/2016/160523_2.html

Add-on lamotrigine enhances bipolar depression treatment

Combining lamotrigine with quetiapine improves the treatment of depressive symptoms in patients with bipolar disorder, with the benefits maintained for at least a year, show findings from the CEQUEL trial.

Scores on the Quick Inventory of Depressive Symptomatology–self report version 16 (QIDS-SR16) at 12 weeks were, on average, 1.73 points lower among 101 moderately depressed bipolar patients randomly assigned to receive lamotrigine (25 mg/day titrated to 200 mg/day) in addition to quetiapine, compared with 101 assigned to receive add-on placebo.

By 52 weeks, the difference was significant at an average of 2.69 points lower for those taking add-on lamotrigine, after taking into account age, bipolar disorder type and dose of quetiapine (< or ≥300 mg/day), the researchers led by John Geddes (University of Oxford, UK) report in The Lancet Psychiatry.

They also found that significantly more patients taking lamotrigine plus quetiapine were in remission at 12 weeks (31 vs 16%) and 52 weeks (36 vs 13%), with relative risks of 2.11 and 3.73, respectively.

Discussing the findings in a related comment, Gin Malhi (University of Sydney, New South Wales, Australia) says: “[T]he investigators skillfully take advantage of the synergy between quetiapine and lamotrigine that arises from their differing, but complementary, mechanisms of action and the separate timescales over which they exert their effects.”

He explains that quetiapine is often given in the short term to ameliorate acute symptoms, whereas lamotrigine is more effective over the longer term. The drug is therefore able to “achieve a therapeutic level and exert its actions under the initial cover of the antipsychotic, which can then be gradually tapered and withdrawn”, he writes.

Add-on lamotrigine enhances bipolar depression treatment

Quetiapine fumarate (Seroquel XR) for Major Depressive Disorder (MDD)....

Quetiapine fumarate (see structure) is marketed by AstraZeneca as Seroquel or SeroquelXR and by Orion Pharma as Ketipinor, is an atypical antipsychotic schizophrenia used in the management of, bipolar I mania, bipolar II depression, bipolar I depression, and used off-label for a variety of other purposes, including insomnia and anxiety disorders.

It is sometimes used off-label, often as an augmentation agent, to treat such conditions as obsessive-compulsive disorder, post-traumatic stress disorder, restless legs syndrome, autism, alcoholism, depression, Tourette syndrome, and has been used by physicians as a sedative for those with sleep disorders or anxiety disorders.

Astra-Zeneca, recently  announced that the FDA has approved once-daily Seroquel XR (quetiapine fumarate) Extended Release Tablets as adjunctive (add-on) treatment to antidepressants in adults with Major Depressive Disorder (MDD). Seroquel XR is the only medication in its class approved by the FDA to treat both major depressive disorder as adjunctive therapy and acute depressive episodes associated with bipolar disorder as monotherapy. The company claims that this approval for Seroquel XR provides physicians with a new adjunctive treatment option for patients with MDD who have an inadequate response to their current antidepressant. FDAs approval of Seroquel XR is based on a clinical development program in MDD involving 939 patients randomized across two studies that assessed the efficacy and safety of once-daily treatment with Seroquel XR as adjunctive treatment to antidepressants.....

Ref : http://www.astrazeneca.com/media/latest-press-releases/2009/seroquel-us-MDD?itemId=7660757