Glumet for the use of weight gain and menstrual problems due to anti psychotics

Glumet is a popular anti diabetic medication. It’s generic name is called Metformin. It is defined as the most popular insulin sensitizer. Use of Glumet is associated with reduction in overall cardiovascular complications in diabetes. In addition, it is used in poly cystic ovarian syndrome (PCOD). In PCOD, it restores menstruation.

Anti-psychotics medications are notorious for their metabolic and endocrine side effects. Especially, second generation anti psychotics such as Olanzapine and Clozapine are known to cause significant weight gain. In addition, Risperidone is notorious for causing menstrual problems such as complete stopping of menstruation. These side effects are common cause for non-adherence of anti-psychotic medications.

Glumet can be used in to treat weight gain associated with Antipsychotics 

Recently concluded randomized double blind placebo controlled clinical trial conducted in china shows evidence for using Glumet in Anti-psychotic induced amenorrhea and weight gain. They compared two groups of women who experienced amenorrhea after antipsychotic treatment. One group was given Glumet 1g per day and other group was given a placebo (dummy medication similar to Glumet in external appearance).

They followed up them for six months. Menstruation was restored in 66% of women (28 women) after six months in Glumet group. Only two women experienced restoration of menstruation placebo group. This is the first study that detected restoration of menstruation after Glumet therapy in patients with antipsychotic induced amenorrhea.

Common Antipsychotics side effects including weight gain : Courtesy  Dr. Stephen M. Stahl. 

In addition, there is significant reduction in body weight and body mass index in Glumet arm of the study.

Most studies that were conducted prior to this also confirm the positive effect of Glumet in anti-psychotic induced weight gain. However, most studies suffer from small sample size. Therefore, studies with larger sample size are needed to conclude Glumet can be used in weight gain associated with anti-psychotic treatment.

Metformin for Treatment of Antipsychotic-Induced Amenorrhea and Weight Gain in Women With First-Episode Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled Study

Fighting weight gain associated with antipsychotics. WEBMD article

Newer anti-depressant with quick action

Ideal antidepressant medication should act quickly, cause fewer side effects and should treat almost all depressive patients with similar efficacy. But current antidepressants are far cry from above ideals.

Antidepressants medications are the most common way to treat depression. Unfortunately around 60% of patients are considered to have resistant depression and antidepressants have delayed action. These patients suffer from depressive symptoms even with medications. One of the reasons for this situation is that scientists and doctors do not exactly know the mechanism of depression in the human brain.

Most of the antidepressants currently in use are developed from molecules identified purely due to chance. For an example imipramine (Tofranil) is the first antidepressant developed. It was identified as having anti-depressant properties purely due to chance and brilliant observation of Roland Kuhn. Imipramine was first tried in patients with schizophrenia. But there was no effect on most of the patients. But a subgroup of patients who had depressive symptoms improved with this medication. It was noted by Kuhn and further studies were performed.

In fact, almost all the antidepressants currently in use have similar efficacy to imipramine. Newer antidepressants have improved tolerability and reduced side effects profile, but without any improved efficacy.

In addition, all the antidepressants have to be taken more than one week to get the antidepressant effect. This is one of the major drawbacks in current antidepressant medications.

Newer rapid acting antidepressant medication

Ketamine is a widely used anesthetic medication. In addition, it is a drug of abuse and in streets it is known as Special K. It was known to cause hallucinations and various psychiatric manifestations. In addition, Ketamine is a powerful Glutamate agonist in the brain.

Now growing clinical trial data suggest Ketamin has quick antidepressant effect. In fact it treats depression within 72 hours.  In addition, it seems to be effective against resistant depression that is not responding to medications and ECT (Electro convulsive therapy). But Ketamine is used only in expert centers.

This effect of Ketamine opens a new door to the identifying true mechanism behind depression. When it is identified, newer antidepressants can be developed with very quick action, efficacy and fewer side effects profile.

Sources

http://www.smw.ch/docs/pdf200x/2007/15/smw-11932.PDF

Use of antipsychotics in patients with dementia and risk of death

Antipsychotic medications are widely used in dementia to control behavioral symptoms. Many studies noted a relationship between increased risk of death among dementia patients and the use of antipsychotics. However, most patients experience difficult to manage behavioral symptoms in dementia and the death may be due to the disease process itself.  

Study published in American journal of psychiatry looked into the mortality among dementia patients who are treated with various anti-psychotic medications. This study compared differences between deaths rates in different anti psychotics using historical data.

According to this study Haloperidol (Haldol) is associated with most number of deaths. Quetiapine (Seroquel) is associated with lowest death rates. Other antipsychotics such as Risperdal, and Zyprexa, lay in-between.

Analysis of this study

However, there is a caveat in this study. It is that this study used archived data. In these data most people with severe dementia were given haloperidol, because some clinicians believed that Haldol is more effective in controlling behavioral symptoms than other antipsychotics. Therefore, naturally they used Haldol frequently in patients with more severe dementia. These patients have high death rates even without any antipsychotics. Therefore, this study may be biased toward newer anti psychotics.

In addition, we need to understand that there are very strong pharmaceutical companies to promote newer antipsychotics. Nobody promotes older antipsychotics such as Haldol even though they are preferable in certain patients.

Journal article in American journal of Psychiatry

Risk of Mortality Among Individual Antipsychotics in Patients With Dementia

Relationship between resistant depression and bipolar disorder

When depression is not responding to one antidepressant medication after giving it for adequate duration and dose then it is refer to as treatment resistant depression. It is a very common problem and in fact up to 50 – 60% of patients with depression can be categorized as having inadequate response (M. Fava et al, 2003).

When depression is not responding to antidepressants then reevaluation of diagnosis becomes very important. One large historical cohort study conducted in Taiwan found a significant relationship between bipolar disorder and treatment resistant depression. It was published in British Journal of Psychiatry 2012 January.

According to this study, history of poor response to antidepressants in unipolar depression could be a useful predictor for bipolar disorder. Around 7.6 -12.1% of those with the diagnosis of unipolar depression was subsequently changed to bipolar disorder. In this group people with treatment resistant depression showed higher rate of change to a bipolar diagnosis (25.6 -26.6%).  This study was conducted from the data of 3500 participants. Data was collected from Taiwan National Health Insurance database. It is a database that covers almost entire (99%) population of Taiwan.

Bipolar disorder can present initially as a depressive disorder. At that time clinicians would diagnose it as a unipolar major depressive episode. But resistance to treatment is a good predictor of subsequent change into bipolar illness. In addition, it would rationalize adding mood stabilizer medication such as Lithium to augment anti depressant medications. Addition of mood stabilizing anti psychotic such as Zyprexa (Olanzapine) also help such patients. 

Symptoms and treatment of atypical depression

Atypical depression is different from the classic depression and many clinicians can miss them. In addition, the sufferer may not identify him or her has depression. But it can carry significant burden. The term and its meaning have changed several times during the past. But currently accepted symptoms of atypical depression are

1.       Variability of mood with reactivity to positive events : - In classic depression mood is profoundly depressed and there is poor mood reactivity. It is especially seen during positive events. They interpret these positive things in a negative light. But in atypical depression there is some reactivity to positive events, making the diagnosis harder.

2.       Overeating: - Unlike classic depression, atypical patients eat more. Eating makes them more comfortable. Classic depression is characterized by loss of appetite.

3.        Over sleeping : - This is also in contrast to classic depression, (In classic depression sleeping is reduced).

4.       Extreme fatigue: - Extreme fatigue with Heaviness in the limbs can be a feature.

5.       Anxiety features such as sweating, palpitations, muscle ache and increased breathing can occur

In addition, personalities with atypical depression tend to sensitive for rejection (real and perceived rejection).

Treatment of atypical depression

Atypical depression is commonly treated with SSRIs or selective serotonin reuptake inhibitors. Tricyclic anti-depressants are not effective in treating atypical depression. (Quitkin et al 1993)