Issue 76, Aug 2018
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Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonized meta-analysis of data from more than 1 million men and women

Ekelund U et al. Lancet. 2016 September; 388(10051):1302-1310. doi: 10.1016/SO140-6736 (16) 30370-1 Epub 2016 Jul 28 PMID: 27475271

Background

Sedentary behavior has been associated with an elevated risk of several chronic conditions as well as mortality. It is unclear whether physical activity attenuates or even eliminates the detrimental effects of prolonged sitting. This study examined the association of sedentary behavior and physical activity with all cause mortality.

Methods

The study included a systematic search of six databases (PubMed, PsychINFO, Embase, Web of Science, Sport Discus, and Scopus) from database inception until October, 2015, for prospective cohort studies that provided data on both daily sitting or TV-viewing time and physical activity. The 16 chosen studies also reported on all-cause mortality, cardiovascular disease mortality, as well as breast, colon, and colorectal cancer mortality. All study data was analyzed after the daily sitting time and TV-viewing time was divided into four standardized groups each and physical activity into quartiles (in metabolic equivalent of task {MET}- hours per week). Then the data across studies was combined to analyze the association of daily sitting time and physical activity with all cause mortality. Hazard ratios were estimated using Cox regression. The analyses were repeated using TV-viewing time instead of daily sitting time.

Results

The sample included 1,005,791 individuals followed between 2-18 years during which 84,609 (8.4%) died. There was a clear dose response association of increased risk of mortality with increased sitting time in combination with low activity level. Compared to the control group (those sitting < 4 hours a day and in the most active quartile), mortality during follow up was 12-59% higher in the two lowest quartiles of physical activity (HR=1.12, 95% CI 1.08-1.16, for the second lowest quartile of physical activity and <4 hours a day of sitting time, HR =1.59, 1.52-1.66 for the lowest quartile of physical activity and > 8 hours/day of sitting time).

Those in the most active quartile but also sitting the most (>8 hours /day) had a significantly lower risk (p<0.0001) of dying during follow up (HR= 1.04; 95% CI 0.99-1.10) than the least active (< 4 hours /day, HR= 1.27,1.22-1.30). The analyses for TV-viewing time was not as precise due to a smaller sample size. For those who watched TV for five or more hours per day, the hazard for all-cause mortality was increased markedly from 16% to 93% across all activity quartiles. In the most active quartile only, watching TV five hours a day was significantly associated with increased mortality (HR 1.16, 95% CI 1.05—1,28). Those in the least active quartile who watched TV for < 1 h/day had a higher mortality risk (HR 1.32, 1.20—1.46; p=0.007)

Conclusions

High levels of moderate intensity physical activity (60-75 minutes per day) seems to eliminate the increased risk of mortality associated with high sitting time. However, this high activity level attenuates, but does not eliminate the increased risk associated with high TV-viewing time. The results provide further evidence on the benefits of physical activity, particularly in societies where increasing numbers of people have to sit for long hours for work and may also inform future public health recommendations.

Clinical Commentary

There is an important body of literature suggesting sedentary behavior increases the risk of chronic ailments and death. In today’s times with the use of devices, smart phones and social media increasing rapidly, sedentary behaviors are increasingly prevalent for long durations of time. This leads to the cliché “sitting is the new smoking”. This is especially true in the developed world. The patients with chronic mental illness are entrapped by both a sedentary lifestyle and excessive TV watching. They rarely have a high activity level. Our patients have a triple whammy, watching TV for long periods, being sedentary and weight gain due to multiple causes. This does not lead to a good outcome. We in the mental health, primary care, and other disciplines need to do more in terms of influencing and changing lifestyles. The key takeaway is sedentary lifestyle and TV watching do not bode well for quality of life (low burden of chronic diseases) and longevity.

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Ketamine for rapid reduction of suicidal thoughts in major depression: A midazolam-controlled randomized clinical trial

Grunebaum MF et al. Am J Psychiatry. 2018 April1; 175(4):327-335. doi: 10.1176/aapi.ajp.2017.17060647. Epub 2017 Dec 5. PMID: 29202655

Background

There is an unmet need for the development of evidenced based medications for the rapid and efficacious treatment of acute suicidal ideation in patients with mood disorders; particularly major depression. Standard antidepressants may lower suicidal ideation in depressed individuals but this takes weeks. Until now treatments such as lithium, clozapine and electroconvulsive (ECT) therapy have evidence of anti-suicidal effects. Randomized clinical trials (RCTs) of intravenous ketamine infusions have provided evidence for rapid reduction of suicidal thoughts and improvement in depressive symptoms. This is a controlled trial in which ketamine and midazolam are compared in suicidal patients with major depressive disorder (MDD). The aim was to assess the effects of ketamine on suicidal thoughts.

Methods

This study (N=80) included subjects with MDD and clinically significant suicidal ideation as evidenced by a score of ≥ 4 on the Scale for Suicidal Ideation (SSI). Responders were defined as ≥ 50% reduction in SSI score.  54% were on antidepressant therapies. They were randomly assigned to receive intravenous infusion of ketamine or midazolam. The outcome was assessed by the SSI score reduction in the ketamine group versus the midazolam group at day1. Subsequently the midazolam non-responders were given open label ketamine infusion.

Results

The ketamine group had a significantly greater reduction in SSI score compared to the midazolam group. (95% CI=2.33, 7.59; Cohen’s d=0.75; p <0.001). The proportion of responders at day1 was 55% for the ketamine and 30% for the midazolam group (odds ratio=2.85, 95% CI=1.14, 7.15). The number needed to treat (NNT) was 4. The ketamine group also had a significantly greater improvement on the depression scales compared to the midazolam group. The effects were maintained for up to six weeks.

Conclusions

Ketamine demonstrated a greater reduction in clinically significant suicidal ideation compared to midazolam.

Clinical Commentary

Ketamine treatment is currently an off-label (not FDA approved) treatment for depression, but studies continue to demonstrate its rapid effects on clinically significant suicidal ideation. This may be lifesaving when given in the emergency room. It should be noted that the antisuicidal effects of these infusions are not long lasting and presently, maintenance ketamine infusions are being done. Currently, there are no validated protocols guiding maintenance ketamine infusions. Psychiatric medications and psychotherapy needs to be optimized to have continued improvement. Hence patients need to be under psychiatric care on an ongoing basis. Safety of the patient is of utmost importance when using this treatment.

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Rates and predictors of conversion to schizophrenia or bipolar disorder following substance-induced psychosis.

Starzer MSK et al. Am J Psychiatry. 2018 April1; 175(4):343-350. doi: 10.1176/aapi.ajp.2017.17020223. Epub 2017 Nov 28. PMID: 29179576

Background

Patients with substance-induced psychosis are commonly seen in the clinical setting. These patients are often treated on an inpatient psychiatric unit and then are discharged to the outpatient clinic. In the outpatient setting clinicians often wonder about the long-term prognosis of these patients. This also begs the question as to how long antipsychotic medications need to be continued for patients whose onset of psychosis was due to substance abuse.

Methods

This study aimed to answer this very question obtaining information from the Danish Civil Registration System and the Psychiatric Central Research Register. Patients (N=6,788) with a diagnosis of substance-induced psychosis over a 20-year time frame (1994-2014) were studied. The follow up was till first diagnosis of schizophrenia, bipolar disorder or until death, emigration, or August 2014 (study termination). The probability of conversion from substance-induced psychosis to schizophrenia or bipolar disorder was determined.

Results

The study revealed that 32.2% of patients with substance-induced psychosis converted to either bipolar disorder or schizophrenia (95% CI=29.7-34.9). The highest rate of conversion was found for cannabis-induced psychosis with 47.4% converting to either schizophrenia or bipolar disorder (95% CI=42.2-52.3). 50% of the conversions to schizophrenia occurred within 3.1 years of the onset of psychosis, while it was 4.4 years for bipolar disorder. Young age was associated with higher risk of conversion to schizophrenia. Self-harm after the onset of psychosis increased the risk of conversion to schizophrenia or bipolar disorder.

Conclusions

Substance-induced psychosis is strongly associated with the development of mental illness, and an extended follow up period is needed to identify the majority of the cases.

Clinical Commentary

This study has important clinical implications. With liberalization of recreational cannabis in multiple states in the US and all of Canada to soon become recreational, an increase in such cases is likely to occur. Based on the findings of this study it may be important for patients to continue antipsychotics over an extended time frame of up to 5 years. This may impact antipsychotic selection too. We would need to consider metabolic issues as well as tardive dyskinesia. This population may be better managed on long acting injectables (LAI) as compliance is enhanced and recurrence risk of psychosis reduced. Finally, the incidence of new onset psychosis is likely to increase significantly, and possibly cases of schizophrenia and bipolar disorder in the long term will increase as well.

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Age-related hearing loss and its association with depression in later life

Brewster KK et al. Am J Geriatr Psychiatry. 2018 July;26(7):788-796. doi:10.1016/jagp.2018.04.003. Epub 2018 Apr 13. PMID 29752060

Background

Age-related hearing loss (ARHL) is the third most common health condition in older adults after heart disease and arthritis. It is often considered by most a benign effect of aging. There have been reports of its association with late life depression (LLD). The aim of this study was to evaluate the relationship between ARHL and late life

Methods

The Health Aging and Body Composition study (N=3075) is a National Institute of Aging project launched in 1997 to assess the change in body composition in older adults and examine the impact of these changes. Subjects were 70-79 years old at baseline and were followed for 10 years. A subset of individuals (N=1204) with hearing information available were chosen and depressive symptoms evaluated over a 10-year time frame using the Center for Epidemiologic Studies Depression Scale (CES-D).

Results

The subjects were divided into two groups; healthy/improving group and impaired/worsening group. The depression trajectory for the impaired/worsening group was 1.63 times the odds of subjects in the healthy/improving group after factoring age, gender, race, and education (p=0.0088, 95% CI, [1.13,2.34]). The odds of having high compared to low depression trajectory for subjects in the impaired/worsening was 1.85 times that in the health/improving group. The primary finding was that ARHL was both cross-sectionally and longitudinally associated with increased depressive symptoms.

Conclusions

ARHL was associated with increased depressive symptoms in older adults. Studies are still needed to address if the treatment of ARHL early may be an effective preventive/therapeutic strategy for depressive symptoms.

Clinical Commentary

In the case of ARHL the research data now supports the clinical notion of associated depression. This longitudinal study with data over a 10 year follow up period suggests that older adults with hearing loss are at increased risk for depression. The implications are clear that hearing loss is a modifiable risk factor for LLD. Older adults should be screened for hearing loss and the issue addressed. Depressed older adults should be screened for ARHL and the hearing loss treated with hearing aids or cochlear implants in addition to medication treatment for depression. On the practical side we know that many older adults with hearing loss do not like to wear hearing aids. Patients with hearing loss often are socially isolated, are frail, and have increased falls.

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Psychological Pain in Suicidality: A meta-analysis.

Ducasse D et al. J Clin Psychiatry. 2017 Aug 29.pii; 16r10732. 79 (3):44-51. doi: 10.4088/JCP. 16r10732. [Epub ahead of print]  PMID:28872267

Background

All of us in mental health as well as other specialties would like to avoid outcomes such as completed suicides or suicide attempts. Suicidality causes a lot of suffering and pain to patients and their significant others. Some patients commonly report they produce physical pain to alleviate psychological pain.  This study includes a meta-analysis to quantify the association between psychological pain and lifetime history of suicidal ideation or suicide attempt.

Methods

The literature search included MEDLINE, Psych INFO, and Web of Science from 1965 to 2015 for (psychache OR mental pain OR psychological pain) AND (suicid*). Observation studies addressing the difference in psychological pain between individuals with and without current or lifetime history of suicidal ideation or suicide attempt were reviewed. Finally, N=20 studies were included.

Results

The data revealed that psychological pain was higher in subjects with lifetime history of suicide attempts and subjects with current suicide attempts versus without (effect sizes = 0.72, P < 10-2 and 0.66, P < 10-2 respectively). In addition, psychological pain was also higher in both subjects with lifetime history of suicidal ideation and subjects with current suicidal ideation versus without (effect sizes =1.49, P=0.01 and 1.15, P< 10-2, respectively). The effect sizes were robust.

Clinical Commentary

These findings have important clinical implications. Psychological pain is a key issue associated with suicidal ideations and attempts. This needs to be addressed for the long term so as to have lasting improvements in these individuals. We may keep them safe in the short-term as inpatients or intensive outpatients but these are only temporary measures. Drugs like lithium and clozapine have established antisuicidal effects. Intravenous ketamine also has been shown to have rapid antisuicidal effects. Psychological pain however will be relieved via cognitive restructuring, improvement in self-esteem and healthy relationships for which competent psychotherapy is a key component of treatment.  

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Sanjay Gupta, MD
Clinical Professor of Psychiatry, SUNY Buffalo

GME Research Review is a monthly newsletter edited by Sanjay Gupta, MD, Clinical Professor of Psychiatry, SUNY Buffalo. Dr. Gupta selects, summarizes, and provides a clinical commentary on the latest published research in psychiatry. 

We are always carefully evaluating which research papers to discuss in GME Research Review. Have come across a research paper published in the last 6 months that you thought is clinically relevant? Do you want me to analyze it for you and for the benefit of others? Please email Dr. Gupta the citation at [email protected]