SSRIs are the first line of treatment in OCD. It is considered that 40% of patients do not respond to SSRI treatment, and that less than 30% of patients experienced substantial symptom improvement.Augmentation with antipsychotics help by blocking the effects of striatal dopamine release which result in improvement of repetitive thoughts and behaviours. Only a third of patients receiving such augmentation benefit from that.We need to look at other ways of augmenting SSRIs. Would medications acting on 5HT3 system be beneficial?
Odansetron modulates dopamine turnover in the nucleus accumbens in the mesolimbic reward pathway.5HT3 receptors are co-localised with GABA interneurons in the ventral tegmental area, and thus can exert indirect inhibitory action on cortico-mesolimbic dopaminergic release. Soltani et al., 2010 reported the results of the first double blind RCT and showed that odansetron is effective in OCD. Odansetron and fluoxetine were started together in this study and hence is not be reflective of the usual augmentation practices.
Stefano Pallantia,Silvia Bernardia, Sarah Antoninib, Nikhilesh Singh and Eric Hollander report the results of the first study to examine efficacy of low-dose ondansetron augmentation to ongoing SSRI therapy in OCD patients who have not adequately responded to SSRI therapy. They also sought to see whether symptoms would recur when the drug was discontinued.
Study: Participants were poor responders to SSRI. ( CGI score of 4 or more, Yale Brown score 24 or more). SSRI doses were moderate to high.(Eg: sertraline 250, fluoxetine 60,escitalopram up to 60). In phase 1 of the trial, participants received oral ondansetron 0.25 mg in twice daily for 2 weeks. Then the dose was titrated to 0.5 mg twice daily for another 10 weeks. During phase II, ondansetron was discontinued and the patients were followed for an additional 4 weeks. Relapse was defined as a worsening of YBOCS total score more than 25% with respect to the last evaluation and/or CGI score = 6–7 after discontinuation.
Results: 21 patients participated in the study. one patient dropped out due to constipation. 57% patients experienced a treatment response at 12 weeks based on 25% improvement in YBOCS score and CGI-I = 1–2. Responders (n=12) reached an average reduction in YBOCS scores of 44%. During the discontinuation phase symptoms worsened by an average of 36.4% in responders. At Week 16, 8 out of 12 (67%) responders relapsed after discontinuation.
Electronic media and electronic case records offer many new ways to conduct affordable and timely research in mental health. The two studies summarised here are examples of an emerging trend.
Rashmi Patel, Nishamali Jayatilleke, Richard Jackson, Robert Stewart and Philip McGuire used the electronic case records of 7678 adults with schizophrenia receiving care in 2011 at Maudsley. A text mining tool was developed using machine learning software to collect information on negative symptoms. Association of negative symptomatology with age, sex, relationship status, impairment of activities of daily living, and (for inpatients) length of hospital stay was studied. 56% had at least one negative symptom. Younger males were particularly at risk. Negative symptoms were associated with more admissions. Emotional withdrawal and apathy were more associated with longer hospital stay.The data suggest that negative symptoms are evident in most patients with schizophrenia and are associated with poor clinical outcomes. Most important conclusion is that large scale electronic data mining is possible with machine learning softwares.
Do tweets containing suicide-related content correlate with actual rates of suicide in an area?
Jared Jashinsky et al analysed the twitter feeds using specific criteria for filtering and identifying potential suicide-related tweets. From these ‘at risk tweets’, ones with location/state were selected. Exclusion techniques were then used to exclude sarcastic/jokes/non pertinent tweets. The proportions of at-risk tweeters per state with respect to the total number of at-risk tweeters were computed. A baseline based on a random sample was also generated for comparison. Between May 2012, to August 2012, a total 1,659,274 tweets from 1,208,809 unique users throughout the world were studied.
Analysis showed an association between rates of tweets by users determined to be at risk for suicide and actual suicide rates. States in the midwestern and western US region and Alaska were observed to have a higher proportion of suicide-related tweeters than expected. These states also have the highest actual rates of suicide.
Text mining/ social media mining offer an affordable and rapid research tool. It can aid in rapid detection of trends in suicidal thinking/suicidal acts. It may also help in detecting individuals with suicidal intentions. This may subsequently provide a platform to improve suicide prevention strategies through timely intervention.
Summary of articles
Tracking suicide risk factors through Twitter in the US. Jashinsky J, Burton SH, Hanson CL, West J, Giraud-Carrier C, Barnes MD, Argyle T. Crisis. 2014;35(1):51-9.
Investigation of negative symptoms in schizophrenia with a machine learning text-mining approach, Rashmi Patel, Nishamali Jayatilleke, Richard Jackson, Robert Stewart, Philip McGuire . The Lancet, Volume 383, Page S16, 26 February 2014
Many small studies have reported that episodes of anger are associated with a transiently higher risk of myocardial infarction (MI), acute coronary syndrome (ACS), ischaemic and haemorrhagic stroke and arrhythmia.
Elizabeth Mostofsky, Elizabeth Anne Penner and Murray A. Mittleman from Harvard report the results of a meta analysis looking at these associations.
They included nine independent case-crossover studies, with 4546 cases of MI, 462 ACS, 590 Ischemic stroke, 215 haemorrhagic stroke and 306 arrhythmia cases. Most studies used ‘Onset anger scale’ to rate the anger. Studies differed in cut off scores for exposure and the methods of collecting information.
There was a 4.74 (95% CI: 2.50 – 8.99; P , 0.001) times higher risk of MI or ACS in the 2 h following outbursts of anger compared with other times. 4 studies included showed heterogeneity in results. However it is safe to conclude that there is evidence of higher MI/ACS risk following episodes of anger.
There was a 3.62 (95% CI: 0.82–16.08; P 1⁄4 0.09) times higher rate of ischaemic stroke in the 2 h following an outburst of anger compared with other times. Heterogeneity between the two studies limit use of pooled estimate of risk.
One study reported a 6.30 (95% CI: 1.60 – 25.0) times higher rate of ruptured intracranial aneurysm in the hour following an outburst of anger.
As these anger outbursts are infrequent and transient, absolute risk increase is small. The absolute risk is higher for individuals with a higher baseline cardiovascular risk and individuals who have frequent outbursts of anger.
Absolute risk is small: Based on the estimate of a 4.74 times higher rate of MI or ACS in the 2 h following outbursts of anger, the absolute impact of one episode of anger per month is only one excess cardiovascular event per 10 000 individuals per year at low (5%) 10-year cardiovascular risk and four excess cardiovascular events per 10 000 individuals per year at high (20%) 10-year cardiovascular risk.
The absolute impact is higher for individuals with more frequent episodes of anger; five episodes of anger per day would result in 158 excess cardiovascular event per 10 000 per year for individuals at low (5%) 10-year cardiovascular risk and a similar frequency of anger outbursts would be associated with 657 excess cardiovascular events per 10000 per year among individuals at high (20%) 10-year cardiovascular risk.
Impact of anger outbursts may be modified by trait anger. It is possible that an individual with an angry temperament is constantly at a relatively high level of physiological activation and is acclimated to the physiological response to anger. Sympathetic activation, haemodynamic changes and stimulation of inflammatory and prothrombotic responses can mediate anger and the above outcomes.
Review establish that there is consistent evidence of a higher risk of cardiovascular events immediately following outbursts of anger. Beta blockers, SSRI and psychosocial interventions may reduce anger outbursts and improve impulse control.
There is a higher risk of MI, ACS, ischaemic and haemorrhagic stroke and arrhythmia in the 2 h following outbursts of anger.
Summary of the article:
Outbursts of anger as a trigger of acute cardiovascular events: a systematic review and meta-analysis. Elizabeth Mostofsky, Elizabeth Anne Penner, and Murray A. Mittleman. European Heart Journal doi:10.1093/eurheartj/ehu033
Patients with social phobia experience negative ‘observer-perspective’ images that represent their inner fears. Earlier aversive social experiences ( ” ghosts from the past”) may be the foundation for these fears. Negative self imagery contributes to maintain the social fear. Changing the self imagery is valuable in treating social phobia. Would imagery rescripting, a technique effectively used to help survivors of childhood trauma, be useful in social phobia as well?
Petra. G. Frets , Ciska Kevenaar & Colin van der Heiden from Netherlands report the successful use of imagery rescripting in this aricle.
Three stages of Imagery Rescripting:
1. Trauma reliving stage: This is the stage asking the patient to relive the original trauma. Patient close their eyes and relive a problematic recent social event in as much detail and as vividly as possible. Patient is then guided to the earlier experience associated with that feeling and ask the patient to relive that i.e. as if it is happening now, in their imagination.
2. Mastery stage: In this stage, along with reliving, patient is visualising the events from the perspective of their current age observing the events and then entering the situation to help their younger self. Therapist guides the patient to find what needs to be done to help their younger self. (”What would need to happen in the image for the younger self to feel better?” or “Is there anything you as the adult would like to do?”)
3. Compassionate stage: This is the last stage where patient relives the rescripted scene from the perspective of their younger self. Aim here is to replace victimization imagery with coping imagery. The adult at this stage is compassionate with affection and soothing words that may enhance the patient’s feeling of being accepted.
The represent study is a case series ( single case design) outlining the application and the effect of imagery rescripting in social phobia as a stand alone treatment.
This preliminary case series suggest that IR as a stand alone treatment is an effective intervention . Number of sessions required varied very much, some requiring 14 or more sessions. It might be more effective in those who report intrusive memories.
This is a small case series, suggesting that imagery rescripting can be beneficial in social phobia. Further rigorous approaches required to confirm the efficacy.
Summary of the article.
Imagery rescripting as a stand-alone treatment for patients with social phobia: a case series.
Frets PG, Kevenaar C, van der Heiden C. J Behav Ther Exp Psychiatry. 2014 Mar;45(1):160-9
Advancing paternal age (APA) at child-bearing is associated with increased risk of many psychiatric disorders in the offspring. Studies have shown that the number of de novo mutations in children depend on age of father at conception. Existing studies have many limitations. ( confounding factors,selection factors (e.g. personality traits associated with postponed parenthood), protective factors (maturity, social and cultural capital associated with late parenthood)). Sibling comparison studies provide the advantage of ruling out genetic and environmental factors shared by siblings. Sibling comparison studies to date show inconsistent findings.
Brian M. D’Onofrio and team of researchers at Indiana university and the Karolisnka institute carried out the largest ever study exploring the link between APA and psychiatric outcomes in offsprings.Association between APA and a range of offspring psychiatric and academic outcomes were studied among all offspring born in Sweden across 28 years. They used sibling comparison as well as numerous other quasi exp designs to calculate/test the hypotheses.
All individuals in the analysis cohort were born in Sweden between 1973 and 2001. 10 national registers/databases were used to extract information. Nearly 90% of swedish population was included in the cohort analysed. APA for each offspring was placed into 7 categories, ranging from 20 years or younger to 45 years or older in 5-year intervals with 20 to 24 years as the reference group.
When accounting for all factors shared by siblings and several measured covariates,parental age of 45 years and older was associated with a 3.5 times increased risk of an offspring having ASD, 13 times risk for ADHD, 2 times risk for psychosis and 25 times risk for bipolar disorder, compared with offspring born to fathers 20 to 24 years old. Multiple sensitivity analysis were carried out to check the robustness of these associations. Specific risks associated with APA follow a dose-response relationship .Unmeasured genetic and environmental selection factors shared by siblings, as well as the influence of several measured covariates, do not account for the associations between APA and offspring morbidity.
Limitations: Observational studies can not prove causality. The sibling comparisons could not rule out within-family confounders associated with APA and the outcomes.
Conclusions: APA represents a risk of numerous mental health outcomes. APA is a greater risk factor for psychiatric morbidity than has been previously reported. Genetic mutations during spermatogenesis associated with APA influence offspring morbidity across numerous indexes of morbidity.
Summary of the article:
Paternal Age at Childbearing and Offspring Psychiatric and Academic Morbidity. Brian M. D’Onofrio, PhD; Martin E. Rickert, PhD; Emma Frans, MSc; Ralf Kuja-Halkola, MSc; Catarina Almqvist, MD; Arvid Sjölander, PhD; Henrik Larsson, PhD; Paul Lichtenstein, PhD . Jama Psychiatry. Ahead of print. Feb 2014.
Most people with suicidal ideas do not act on them. Our understanding of the transition from suicidal ideas to action is very much limited. David Klonsky & Alexis May from the British Columbia University explores this subject in this months editorial.
A large population-based study from Netherlands (ten Have et al 2009) reported that only 7.4% of those with baseline suicidal ideation reported a suicide attempt over the subsequent 2 years. Differences between ideators and attempters is an area of key knowledge that is lacking. Kesler et al , after analysing the National Comorbidity Survey (Kessler et al., 1999) reported that “all significant risk factors … were more strongly related to ideation than to progression from ideation to a plan or an attempt”. Odds Ratios were quite high for distinguishing suicide ideators from those who have never been suicidal i.e. individuals with such conditions as depression were more likely to have suicidal ideas. In contrast, the odds ratios for distinguishing attempters from ideators were very low. Other studies have also confirmed this pattern.(e.g.: Borges, & Ono, 2012, Nock et al., 2013).
Hopelessness has long been emphasized as an important suicide risk factor, however this also fail to differentiate between ideators and attempters (Acosta et al., 2012 etc).
Would impulsivity explain the transition? It has been mentioned that individuals high on impulsivity are “more likely to act on suicidal feelings” and as “a more significant indicator of suicide attempt than the presence of a specific suicide plan”. Empirical findings do not support this notion. In a large military sample, impulsivity was equivalent between attempters and ideators (Klonsky & May, 2010).
Theoretical context of this differentiation come from Joiner’s interpersonal theory of suicide which states that perceived burdensomeness and low belongingness combine to create suicidal desire, whereas the capability to act on desire is acquired over time through exposure to painful and provocative events (Van Orden et al., 2010) .Rory O’Connor’s motivational– volitional theory of suicidal behaviour also stress on capability with focus on dispositional pain sensitivity and physical access to lethal means as additional factors.
Authors suggest that ‘ideation- to-action’ framework should be used in studying risk factors and processes in suicide. They stress the need to better understand progression from ideation to attempts.
Summary of the article:
Differentiating suicide attempters from suicide ideators: a critical frontier for suicidology research.
Klonsky ED, May AM. Suicide Life Threat Behav. 2014 Feb;44(1):1-5