“decade of life lost”: excess mortality due to mental disorders. JAMA Psych. ahead of print.2015


Burden of mental illness is growing worldwide. It is widely known that mental disorders are associated with excess disability as well as excess mortality.

Elizabeth Reisinger Walker,Robin E. McGee & Benjamin G. Druss from Emeroy University report the results of a meta analysis of studies looking at excess mortality in mental disorders.

Comprehensive search ( up to 2014)  was carried out to identify all cohort studies that used appropriate methods to identify mental disorders and  where outcomes ( mortality) were reported in comparison to control/ general population . They estimated one estimate of risk from each study analysis. 203 studies met all criteria.These came form 29 countries. Mental disorders were mostly identified from medical records or administrative data .Quarter of studies did this by diagnostic interviews. Follow up ranged between one to 52 years, with a median of 10 years.


The overall pooled Relative Risk for mortality among people with mental disorders was 2.22 (95% CI, 2.12-2.33). All-cause mortality was significantly elevated for psychoses, mood disorders, and anxiety.Mortality risk for psychoses was significantly higher than those for depression,bipolar disorder , and anxiety.Analysis of natural causes of death resulted in a pooled RR of 1.80 . For unnatural causes, the pooled RR from 106 studies was 7.22.The authors estimate that 67.3% of deaths were due to natural causes and 17.5% were due to unnatural causes, with the remainder being unknown or unidentified.

The reduction in life expectancy ranged from 1.4 to 32 years, with a median of 10.1 years .

8 million deaths worldwide are attributable to mental disorders each year.


People with mental disorders have a mortality rate that is 2.22 times higher than the general population or people without mental disorders, with a decade of potential life lost.

Estimation of Population Attributable Risk show that nearly 15% of deaths worldwide, (= 8 million deaths each year), are attributable to mental disorders.

Natural causes accounted for more than two-thirds of deaths among people with mental disorders, suggesting that physical health problems ( like Cardiovascular health) requires much more attention. Behavioral and lifestyle factors, access to and quality of health care, and social determinants of health, such as poverty and social connectedness, all are important factors contributing to this excess mortality among mentally ill.

Summary of the article:

Mortality in Mental Disorders and Global Disease Burden Implications A Systematic Review and Meta-analysis.  Elizabeth Reisinger Walker, PhD, MPH, MAT; Robin E. McGee, MPH; Benjamin G. Druss, MD, MPH. JAMA Psychiatry.  Published online February 11, 2015.

Can quality improvement programs help to reduce polypharmacy? Therapeutic Adv psychhopharmac. 2015.feb.


High dose antipsychotic therapy as well as poly pharmacy are common practices despite lack of evidence to support such uses. Royal college of Psychiatrists (UK) recommended that high dose should be used only after other evidence based strategies have failed.Regular use of combinations of antipsychotics are discouraged by NICE (UK).

Can quality improvement programs change the prescribing behaviours?

Shubhra Mace and David Taylor from SLAM ( Maudsley) report the results of their 6 year long quality improvement program. Baseline data  on high dose and multiple antipsychotic use was collected in 2006. The first quality improvement step was to issue guidance on prn ( as required ) use of antipsychotics. PRN was to be avoided , and if at all prescribed, needed to be reviewed every week.PRN prescription needed to  be more detailed as well.This was disseminated across the hospital. Since 2007, high dose and combination uses were monitored by pharmacy.  Prescribers needed to record rationale and do the necessary additional monitoring . During the next few years, these guidances and tailored exercises were repeated. Regular prescription reviews and discussions were implemented. Final survey was in 2012.


High dose prescribing decreased from 58% to 10%. polypharmacy decreased from 57% to 16%. These are impressive achievements. The national percentage of high dose prescription is 28%. National percentage of combination therapy is 38%.

The high dose calculation include 24 hr PRN prescription as well. PRN prescribed may not be given to patients. PRN use accounted for majority of the polypharmacy. Prn use is common place. Patients might be on only one regular antipsychotic, but would be written up for another antipsychotic for PRN use. clinicians in acute inpatient units would argue that the as needed prescription is very useful in controlling disturbed behaviour. However, the re audit at SLAM show that prescribers are less using as required antipsychotics for such purposes after the intervention.

There is some evidence to support combination antipsychotic use. The program set the target rate of prescribing high doses and combinations of antipsychotics on individual units to be below 20% .

Why 20%? : If 60% of all those with psychosis are treatment resistant  (then  they should be tried on clozapine) and 30% of them ( i.e. on clozapine)  are not responding to  clozapine alone adequately, there will be 18% requiring addition of second antipsychotic to clozapine.

Authors highlight the issue of initial resistance from prescribers to proposed changes. Support from top of the organisation was crucial.Persistence with quality targets was important.Benchmarkung and peer review were useful approaches to encourage prescribers to adopt the changes.

Comments: High dose monitoring form as recommended by Royal College is in widespread use in UK. Clinicians are more aware and patients are perhaps more vigilant of adverse effects of antipsychotics, particularly of higher dose/combinations. Changes in PRN use policy would further help to reduce polypharmacy.

Summary of the article:

Reducing the rates of prescribing high-dose antipsychotics and polypharmacy on psychiatricinpatient and intensive care unitsresults of a 6-year quality improvement programme.

Mace S, Taylor D. Ther Adv Psychopharmacol. 2015 Feb;5(1):4-12

Can Smell tests help in early identification of Alzheimer’s disease? Current Opinion. March.2015


Alzheimers disease (AD)  has an insidious symptom onset.Though biomarker research has advanced, they are not yet readily available  for clinical use. Are there any simple clinical test that can reveal the onset of AD?

Latha Velayudhan reviews this question in current opinion.

Almost all studies in this area have shown that AD patients always have smell defects. Defects in smell identification ( example :  University of Pennsylvania smell identification test (UPSIT)) is shown to correlate with MMSE scores. Smell identification tests have been able to differentiate AD from controls.

A three item olfactory identification test could differentiate between AD and depression.

It is also shown that such changes in olfaction can help in predicting conversion from  MCI (Mild cognitive impairment )  to AD when combined with other measures like functioning report,  verbal memory, and hippocampal- entorhinal cortex volumes. 

Olfactory function is overlooked by clinicians and by patients. Patients are largely unaware of their deficits. Low olfaction score patients, especially those unaware of smelling problems, are most prone to developing Alzheimer’s disease.Olfactory identification and recognition are the most interesting candidates to be included in a battery to detect subclinical cases in Alzheimer’s disease.

These tests are inexpensive, simple and can be applied bedside. Day to day utility in clinical practice  is yet to be established.

Summary of the article:

Smell identification function and Alzheimer’s disease: a selective review.

Velayudhan L. Curr Opin Psychiatry. 2015 Mar;28(2):173-9


Are medications effective in Autism? Current Opi Psy.March.2015


Autistic spectrum Disorders (ASD) affect 1% of population.Along with the core difficulties (defective reciprocal communication & repetitive behaviour), they also suffer from anxiety, aggression, self injury , mood symptoms etc. Generally, these individuals do not respond favourably to antipsychotics. They tend to experience more side effects than others. Despite these , a good proportion are treated with antipsychotics.

Na Young Jia,and Robert L. Findling review the recent evidence for medications in ASD.

Risperidone  and aripiprazole are approved by FDA for problematic irritability in ASD.They could reduce stereotypy and hyperactivity.Use is recommended to be reserved for severe problems only. Antipsychotics do not have any effect on communication defects. Olanzapine can also improve behavours but risk of metabolic effects are more than the other two medications.

Stimulants: Atomexetine  may offer benefits when ADHD symptoms dominate ASD.It may take longer time for benefits of atomexetine to be seen. Methyl phenidate has also been tried in trials- response rates are generally lower than in ADHD.

Antidepressants: There is no evidence to support SSRI use in ASD. In fact evidence of harm is present.

Antiepiletics: no evidence to suppport use in ASD.

Others: Medications acting on GABA, glutamate, cholenrgic systems- so far no good news. Oxytocin has attracted lot of interest and several trials on ongoing. However two recent trails in children reported no improvement in emotional  cognition or social behaviours .

Conclusion: No medication is shown to be effective in treating the core symptoms of ASD. Nonpharmacologic options such as modifications in the setting and behavioral interventions may improve target symptoms. Severe problematic irritability can be treated with either risperidone or aripiprazole.

summary of the article

An update on pharmacotherapy for autism spectrum disorder in children and adolescents.

Young N Ji, Findling RL.Curr Opin Psychiatry. 2015 Mar;28(2):91-101.

What factors correlate with completed suicide in bipolar disorder? bipolar disorders.Feb.2015


Bipolar disorder (BPD) is associated with  the highest suicide rate among mental disorders. Between 5%-8% ob those with BPD can complete suicide during an 18 years follow up period. Standardised Mortality Rate (SMR)  is 10-30 fold than that in general population. It is also  estimated that up to half will attempt suicide during life time.

International Society for Bipolar Disorder carried out a metaanalysis of  literature on correlates of suicide/attempts in bipolar disorder. The comprehensive search with clearly defined inclusion criteria identified 1700 abstracts of which 44 studies met all criteria to be included in the analysis.


Factors correlated with suicide attempts: women, early onset of disorder, depression as onset episode, comorbid anxiety/substance use/cluster B personality disorder and family history of suicide.

Factors correlated with suicide: male gender and first degree family history of suicide.

Bipolar 1 or 2 and presence of psychosis were not particularly associated with suicidal behaviours.

Limitations: Presence of variables in relation to time span/ proximity to outcome is not known ( i.e. life time anxiety disorder as comorbid condition may not mean that  comorbidity  was present at suicide. Both prospective and retrospective studies were included, hence focus is on correlation than risk prediction. Many factors of importance may be excluded ( e.g. past suicide attempt) because of insufficient studies  with  required data.


Most of these findings reflect the experience of practising psychiatrists. These generally confirm what we know already. Depressive polarity ( first episode with depression) is associated with higher suicide attempts. It is possible that those who present with depression face delay in diagnosis ( as bipolar) and this might be contributing to the increased morbidity.

The OR of  suicide among male gender is 1.8 as opposed to female gender.The difference between genders is not wide enough to be used in clinical practice to inform our risk assessments / predictions. The accompanying commentary by Barthge CA concludes rightly: There is no marker indicating that a patient can be considered safe ( with regard to completed suicide).

Summary of the article:

International Society for Bipolar Disorders Task Force on Suicidemeta-analyses and meta-regression of correlates of suicideattempts and suicide deaths in bipolar disorder.

Schaffer A, Isometsä ET, Tondo L, H Moreno D, Turecki G, Reis C, Cassidy F, Sinyor M, Azorin JM, Kessing LV, Ha K, Goldstein T, Weizman A, Beautrais A, Chou YH, Diazgranados N, Levitt AJ, Zarate CA Jr, Rihmer Z, Yatham LN. Bipolar Disord. 2015 Feb;17(1):1-16.

Are Psychiatrists not good role models for medical students? Act Psych. jan.2015


Psychiatry is not a particularly desired specialty choice among medical students. A UK study among medical students highlighted some factors that discouraged them from choosing psychiatry: 1.poor prognosis of psychiatric patients (20%) 2. Poor scientific basis of psychiatry (18%) 3. Perceived lack of an evidence base (14%). (C Barton 2011). Many  negative attitudes are part of the wider population perceptions  (about  mental disorder as well as about those who work with them).

Medical teaching faculty’s opinions and ideas are also possibly influencing medical students choices.  Stuart H, Sartorius N, Liinamaa T ( the Images Study Group) asked medical faculty ( non psychiatric) in 15 academic units in UK Europe and Asia. A 37 item questionnaire was used to collect information.

Questions covered key areas:  perceptions of psychiatry as a discipline , perceptions of the effectiveness of psychiatric treatments , perceptions of psychiatrists as role models , perceptions of psychiatry as a career, perceptions of psychiatric patients and perceptions about the quality of psychiatric training. Survey response rate was 65%.


Medical school culture did not view psychiatry as an exciting, rapidly expanding, intellec- tually challenging, or evidence-based branch of medicine. Most thought that psychiatric patients should be treated in specialist centres outside general hospital setting.Majority thought that psychiatrist in their medical schools were not good role models. 20% thought psychiatrists have too much powers and that treatments were not effective.10% thought that psychiatrists medical skills were poor.As a career, psychiatry was seen as having low prestige relative to other specialties.

20% thought that students who went to psychiatry chose it because of their own problems or because they could not get in to other specialties.

Reasons like psychiatry patients are emotionally draining, not appreciative of care provided etc also surfaced in the negative view.

The extent and depth of negative views among academic medical colleagues are alarming. Many other studies have shown that negative comments from significant others have an enormous impact on career choices.


Psychiatry need to do a lot of work to improve the understanding  among the ” physical health” colleagues to change this very negative image. Addressing specific negative themes   should be part of such work. The stigma of psychiatry is still very much alive among medical colleagues.

Summary of the article:

Images of psychiatry and psychiatrists: Acta Psychiatr Scand 2015: 131: 21–28

Do antipsychotics alter functional connectivity of brain? JAMA ps.Jan.2015


Abnormalities in corticostrital connections is  considered to be fundamental pathology in Schizophrenia. Changes in blood flow and  dopamine levels have been repeatedly demonstrated in schizophrenia previously. Functional connectivity studies aim to study activation levels in the key regions. Altered functional connectivity between striatum and cortical regions can be seen as   a risk phenotype in patients with first-episode psychosis (FEP) and their relatives.

What is the effect of antipsychotic medications on the  cortico stratal functional circuitry ? How does it relate to symptom changes?

Deepak K. Sarpal and colleagues from US  examined the relationship between changes in striatal circuitry and reduction in psychotic symptoms after treatment with antipsychotic medication ( risperidone or aripiprazole)  with first episode of Schizophrenia. Patients  ( 15-40 age group) and controls were scanned at baseline. After 12 weeks of antipsychotic treatment ( aripiprazole or risperidone) patients were scanned again and were compared with control scans at 12 weeks. Particiapnts were diagnosed by structured interview, they had less than 2 weeks of cumulative antipsychotic exposure ( life time) prior to entry to the study. BPRS was used to rate symptoms.All patients received double-blind treatment with either risperidone (dose range, 1-6 mg) or aripiprazole (5-30 mg) for 16 week.


With improvement of psychosis researchers  observed a significant increase in functional connectivity between the right dorsal caudate and several pre- frontal regions including the anterior cingulate, right dorsolateral prefrontal cortex, and orbitofrontal cortex. Improvement of psychosis was associated with alterations in functional connections of the striatum. Striatum is often implicated in the pathophysiology of psychosis and is rich in  D2 receptors.

Significantly increased connectivity between striatal regions and the dorsal anterior cingulate implicated a role for error monitoring and cognitive control in recovery from psychotic symptoms.Functional coordination between the striatum and pre frontal and limbic systems may influence salience processing as psychotic symptoms are reduced.

Lui and colleagues 2010 found that  SGAs increased the amplitude of low-frequency fluctuations (ALFF) of blood oxygen level-dependent signals in prefrontal and parietal cortex, left superior temporal cortex, and right caudate nucleus. An association with reduction of clinical symptoms were also noted.Prospective nature of the present study adds greater interest in its observations.


It is important to note that in this study there was no baseline difference between the two groups in functional connectivity. Functional circuits are under more scrutiny and are probably key in understanding how symptoms appear as well as respond to medications.

Summary of the article: 

Antipsychotic treatment and functional connectivity of the striatum in first-episode schizophrenia.

Sarpal DK, Robinson DG, Lencz T, Argyelan M, Ikuta T, Karlsgodt K, Gallego JA, Kane JM, Szeszko PR, Malhotra AK.

JAMA Psychiatry. 2015 Jan 1;72(1):5-13