What matters for population well being? GDP or Gini? Jl of happiness studies. July.2014

23.07.2014

What factors decide/ influence/ define that a society a ‘better’ one ? Economists argue that GDP is a good measure of well-being of a population.over the many years, social scientists have expanded the idea of wellbeing to include satisfaction with career, social interactions, financial status, physical health, life evaluation, emotional health, work environment, access to basic needs.. to mention a few. Rawl’s theory ( justice) focus on the redistribution of wealth to equalize access of opportunities and provision of public/social goods. The fact that countries with progressive income taxes measure better on wellbeing is very much supportive of this theory.

US, richest country in the world, is well behind in terms of wellbeing. Many studies using US data, have confirmed that it is relative wealth/ income that is more important ( than absolute ) and income disparity with in a community is excessively corrosive for wellbeing of the whole community.

Vivian Grace Valdmanis of the Health Policy and Public Health at Philadelphia analysed well-being in each of the fifty states in the US using a mixed panel model approach (2009–2011) including typical economic and political measures.

Results:

1. Well-being is positively and statistically significantly correlated with the Gini coefficient i.e. the more the income inequality in a state, less well-being it has.

2. The more politically conservative a state is, less is the well-being.
3. Per capita income itself did not explain the well-being differences. it is likely that post 2008 economic state might have unduly influenced this. However Gini index was a sensitive measure explaining wellbeing.

This is not a new finding. Inequality with in a society has harmful effects on population well-being. Political conservatism also limits wellbeing of the population.

Comment: In countries where all focus is on economic growth ( i.e. GDP), neglecting “Gini” could have serious and long-lasting negative consequences.

Summary of the article

Vivian Grace Valdmanis.Factors Affecting Well-Being at the State Level in the United States.J Happiness Stud. DOI 10.1007/s10902-014-9545-0

Do psychotherapy reduce relapse rates in depression? Jl Aff disorder. July.2014

21.07.2014

Depression is a highly recurrent disorder. Rates  of recurrence range between 35% and 85% over a time span of 15 years  depending on nature of the sample. Psychotherapy is effective in depression in short or medium term. However some studies suggest that half of patients who responded to such therapies relapse in two years though CBT is found in some studies as providing more enduring effect.

Christiane Steinert  and colleagues asked the question: In studies of sufficient follow-up ( i.e. more than two years), what is the overall likelihood for a depressive relapse post therapy? 

The search was comprehensive and the PRISMA guidance were adhered to. All RCTs on  Adult unipolar non psychotic depression  where psychotherapy was compared against a non-psychotherapeutic comparison condition  were included. From 2985 abstracts 60 were subjected to full review and 11 were included in the meta analysis.

Results

Long-term follow-up data were available for 966 patients. Follow-up times varied between 34 and 72 months post-therapy, with an average of about 4.4 years. All patients in the comparison conditions received some form of active alternative treatment (pharmacotherapy or some form of psychotherapy ) that was designed not to contain ingredients that are specific for psychotherapy.

Pooled overall event rate  ( observer rated relapse ) was 0.39 (95% CI 0.29, 0.50 ). Self-reported non-remission of the sample was  0.43 (95% CI 0.33, 0.53)  i.e. about 40% of patients previously treated with psychotherapy had at least one relapse (or were still judged as depressed) by the end of the follow-up. Heterogeneity of results was large ( i.e. much of the observed difference between study results were due to non random differences between studies. i.e. quality, methodology, sampling etc ).

 0.53 (95% CI 0.37, 0.68) of patients in the psychotherapy conditions and 0.71 (95% CI 0.58, 0.82) of patients in the non- psychotherapeutic comparison conditions had a relapse.  Resulting NNT was 6 i.e.  6 patients had to be treated with psychotherapy to achieve one less relapse as compared to other treatments.

Limitations: Though most studies were graded as good quality,  studies scored poorly on treatment integrity and therapist competence.  All studies were originally designed as RCTs, but  the follow-up of most of these trials has to be regarded naturalistic. Five studies only followed-up patients who were remitted after receiving different kinds of treatment in the first place.ie non-remitted patients were excluded from the follow-ups undermining the RCT’s core assumptions. Psychotherapy was delivered in different stages of a depressive disorder (remission, episode) and this limits comparability.

Conclusions: On average of 4.5 year follow-up, 40% of patients experienced a relapse post therapy. Psychotherapeutic interventions yielded a more favorable long-term outcome. Results has to be interpreted with caution given the limitations.

Summary of the article: 

Relapse rates after psychotherapy for depression – stable long-term effects? A meta-analysis. Christiane Steinert , Mareike Hofmann , Johannes Kruse , Falk Leichsenring. 2014. Journal of Affective Disorders 168 (2014) 107–118. ( Online: July 2014)

 

Is serum BDNF concentration a peripheral marker of depression? Molecular Psych.2014.July.

04.07.2014

Neurotrophin hypothesis of depression was originally formulated in 1997 by Duman, Heninger and Nestler. Stress induced aberrations in neural plasticity is thought to result in depression. This is reflected in lower BDNF . Antidepressants increase the BDNF levels and correct this aberration. In 2002 , low BDNF was shown in depressed patients (Karege et al. 2002). In 2003, an increase in BDNF with antidepressant treatment was demonstrated (Shimizu et al 2003). Meta analysis have  confirmed these observations.

Molendijk  et al report current state of knowledge by a new meta analysis . From 55  studies, they  extracted 124 between-group effect- size estimates and 55 correlation coefficients.

Results

Antidepressant-free depressed patients had lower BDNF concentrations as compared with healthy controls (d=  0.71, 95% CI = -0.89 to  -0.53).  Heathy controls and antidepressant treated groups did not differ in BDNF levels. Higher symptom severity was associated with a lower BDNF levels in untreated patients. 

Differences were still significant after correcting for publication bias.

The effects sizes are smaller than previous analysis , mainly due to  adjusting for between-study heterogeneity and publication bias.

This analysis confirms that  altered serum BDNF concentrations are peripheral manifestations of depression.  Authors raise the possibility that BDNF  cab  used  as a treatment biomarker helping us to predict the outcomes.  Another interesting question: What is the difference between pro and mature BDNF as it is thought that they have opposing actions. Would the ratio tell us more about depression or  treatment response ?

 Summary of the article: 

Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484).

Molendijk ML, Spinhoven P, Polak M, Bus BA, Penninx BW, Elzinga BM. Mol Psychiatry. 2014 Jul;19(7):791-800.

Can antibiotics cause Psychosis? J Clin Psychopharmacol. 2014 Aug.

03.07.2014

Psychotic symptoms emerging after use of antibiotics  have been reported occasionally.  This include psychosis as well as mania with psychotic symptoms ( = antibiomania). Penicillin associated psychosis  is also known as Hoigne syndrome.  How antibiotics cause psychosis is not well understood. It is possible that GABA antagonism ( mainly by fluroquinolone ) , inhibition of prostaglandin synthesis ( = increase in dopamine) , and N-methyl-D-aspartate (NMDA) receptor hypo functioning ( due to depletion of D alanine producing intestinal flora) may be involved.

Infection itself can be associated with psychotic symptoms. UTI in the context of delirium and dementia is a well-known/ common example. Studies suggest that UTI can be the commonest cause for unrecognised medical condition on admission in geriatric patients with psychotic symptoms.

Safinaz Mostafa, and Brian J. Miller conducted a systematic review of cases of antibiotic-associated acute psychosis during treatment of a UTI and evaluated the strength of the association for each case using the guidelines for evaluation of drug-associated events.

They identified 15 cases of antibiotic- associated psychosis during treatment of UTI. These were associated with: fluoroquinolones (n = 8), trimethoprim-sulfamethoxazole  (n = 5), and penicillins (n = 2). Patients were on antibiotics for a mean 4.8 days before psychosis emerged. Two had a previous history of antibiotic related psychosis. All patients had some form of psychiatric history.

Psychotic symptoms included hallucinations (n = 12),  delusions (n = 9), disorganization (n = 5), and catatonia (n = 3) .

80% of cases with trimethoprim- sulphamethoxazole was considered as  highly suggestive of causation. 60% of all cases were considered as  strongly suggesting antibiotic to cause psychosis. 33% were moderately suggestive of this.

In most cases onset and resolution of psychosis occurred within 1 week of initiation or discontinuation of the antibiotics.  Half did not require antipsychotic treatment. In 3 cases, a recurrence of psychosis after re challenge with the same antibiotic provides strong support to the notion that antibiotics could cause psychotic states.

Limitations: Small case series. Cases associated with UTI treatment alone included.

Summary of the article:

Antibiotic-associated psychosis during treatment of urinary tract infections: a systematic review.

Mostafa S, Miller BJ. J Clin Psychopharmacol. 2014 Aug;34(4):483-90

Do statin reduce depression risk ? J Affective Disorders. 2014.May.

30.06.2014

Statins are widely prescribed. Side effects as well as benefits of statins have recently been a focus of hot debate. Low serum cholesterol has been associated with antisocial personality, violent behaviour, suicide, and aggressive conduct. Depression is also considered as a possible consequence of statins. Although  many studies have reported benefits of statin in depression , negative associations  have also been reported.

Do statins increase the risk of depression?

Ajay K. Parsaik et al report the results of a comprehensive meta analysis  answering this question in this article. They included all comparative studies of any design . Newcastle–Ottawa Scale was used to assess quality of non randomised studies .From initial search yield of 979 articles only 7 were included in the final analysis. Analysis thus had  a total of 9187 participants.  Mean age of participants were 64+ -5 years.

Results:

Overall pooled OR for depression among statins users was 0.68 (95% confidence interval 0.52–0.89) indicating  protective effect of statins against depression. Modest heterogeneity was observed between the studies ( 55% of difference between study results were due to true differences rather than chance/random).Exclusion of one particular study contributing to this  did not change the pooled effect much.

Limitations: Adjustment for confounders varied across the studies. All studies used different scales for reporting depression.

How statin might work? Ability to reduce oxidative stress and inflammatory cytokines may be the basis of this association.

Conclusions: Statin users are less likely to be depressed.statins have a protective effect on depression.

Summary of the article:

Statins use and risk of depression: a systematic review and meta-analysis.

Parsaik AK, Singh B, Hassan Murad M, Singh K, Mascarenhas SS, Williams MD, Lapid MI, Richardson JW, West CP, Rummans TA.

J Affect Disord. 2014 May;160:62-7

Did FDA warning on antidepressant associated suicidal behaviour reduce suicide attempts? BMJ. June.2014

24.06.2014

The risk of antidepressant induced   suicidal ideas in children and  young adults has been a controversy since 2003. In 2004, FDA added this as a black box warning  on all antidepressants. The meta analysis FDA used included studies that were not designed to examine these effects. Relative risk for suicidal behavior or ideation in this meta analysis  was  1.95 (95% confidence interval 1.28 to 2.98) for young people treated with antidepressants compared with those given placebo. Suicide is the third leading cause of death in 15-24 age group and antidepressants are widely used to treat depression/ suicidal behaviours. Antidepressant use fell significantly following FDA findings.

Christine Y Lu  et al investigated  how the FDA recommendations changed the prescription of antidepressants as well as suicidal behaviours in  11 US health care organisations, who serves members who are generally representative of each system’s geographic service area . The percentage of enrollees who were dispensed an antidepressant was calculated for adolescents , young adults and adults. An interrupted time series analysis  ( i.e. this method can control for secular trends whether the fad warnings caused abrupt changes in the level or the pre-existing trend of  suicidal behaviours). The cohort had 1.1 million adolescents, 1.4 million young adults, and 5 million adults per quarter.

Findings:

1. Adolescents: FDA warnings caused an abrupt decline in the previously upward trend of antidepressant use by adolescents. In the second year after warnings, relative reduction of 31.0% in antidepressant use was noted. This coincided with a relative increase of 22 % in psychotropic drug poisonings in the second year after the warnings. There were no differences in completed suicides.

2.Young adults: Similar to adolescents a relative reduction of 24 % in antidepressant use in the second year after the warnings  was observed along with a relative increase of 34 % in psychotropic poisoning the second year after the warnings . Completed suicide rates remained stable.

3.Adults: Antidepressant use showed a relative reduction of 14.5% , this coincided with a statistically insignificant increase in psychotropic poisoning.

Results were consistent across different areas. Similar findings are reported by others before. The downward trend of antidepressant use stopped in 2008, possibly following 2007 modified recommendation ( i.e. asking prescribers to consider risk of  not treating mood disorders) from FDA.

Limitations:  Only third of suicidal attempts are medically treated and the data is of those who were treated. ( this could have under estimated the suicidal attempts).  Psychotropic drug poisonings account for about 38% of suicide attempts, the results underestimate increases in suicide attempts after the warnings.

Conclusions:   Restricted antidepressant use was associated with  increased rather than decreased suicide attempts. Regulatory warnings may have unintended consequences. It is important to monitor population level effects of such warnings.

Summary of the article: 

Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coveragequasi-experimental study.

Lu CY, Zhang F, Lakoma MD, Madden JM, Rusinak D, Penfold RB, Simon G, Ahmedani BK, Clarke G, Hunkeler EM, Waitzfelder B, Owen-Smith A, Raebel MA, Rossom R, Coleman KJ, Copeland LA, Soumerai SB. BMJ. 2014 Jun 18;348:g3596.

How common is Metabolic syndrome in depression? Psycho Med. 2014.June.

19.06.2014

Individuals with depression have  twice the risk of developing CVD. Depression  increase the risk for cardiac mortality 2-4 times. Background socio economic and  life style factors are linked to this increased risk. Reduced uptake of screening, not receiving good quality physical care, poor compliance with treatments, medication effects, smoking, inactivity , depression associated changes in physiology all contribute to this.

It is important to identify risk factors in routine care of depression. The concept of metabolic syndrome (central obesity, high blood pressure, low levels of high density lipoprotein cholesterol (HDL-C), elevated triglycerides and hyperglycemia ) help clinicians to focus on risk factors and address them appropriately.

How common is Metabolic syndrome among individuals with depression? 

D. Vancampfort et al report the results of a meta analysis on this question. All studies (case–control studies, prospective cohort studies, cross-sectional studies and comparisons of study populations with age standardisation ) where depression was diagnosed using DSM or ICD criteria and Met S  diagnosed according to existing criteria ( either WHO, IDF or ATP) were included.

Results

18 studies met criteria  with the total data set having 5531  individuals . Studies included both out patients and inpatients. Weighted mean prevalence of MetS  was 30.5% (95% CI 26.3–35.1).  Use of different MetS criteria did not make any significant difference. 40% of individuals with MDD had abdominal obesity. About 30% had abnormal HDL-C or triglycerides, and 20% had significant pre- diabetes (using the > 110 mg/dl fasting glucose threshold for hyperglycemia).

There was no significant difference between men and women

Age did not explain differences in prevalence estimates.

 whether illness duration had a moderating effect was not investigated.

No relationship between antidepressant use and MetS prevalence was found  but conclusions on this cannot be made with present data.

Use of antipsychotics was a significant moderator for increased prevalence of MetS.

Limitations:

Methodological heterogeneity across studies. (random-effects models used).  Studies with less than 50 participants were excluded.

Conclusions: Odds for MetS are 1.5 times higher for persons with MDD compared with general population controls. Individuals with depression are at a high risk for Met S.

Comments: All patients diagnosed with depression should be monitored for met S.

Summary of the article: 

Metabolic syndrome and metabolic abnormalities in patients with major depressive disorder: a meta-analysis of prevalences and moderating variables.

Vancampfort D, Correll CU, Wampers M, Sienaert P, Mitchell AJ, De Herdt A, Probst M, Scheewe TW, De Hert M. Psychol Med. 2014. June.