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Issue 77, Sep 2018
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Causes of death after nonfatal opioid overdose.

Olfson M. et. al. JAMA Psychiatry. 2018 Aug; 75 (8):820-827 Jun 20. doi: 10.1001/jamapsychiatry.2018.1471. [Epub ahead of print]

Background

There has been a substantial increase in opioid associated emergency department visits and hospital admissions. A number of these presentations are nonfatal opioid related overdoses. There is an increased mortality in this population. The aim of this study was to evaluate the mortality within 1 year of the nonfatal opioid overdose.

Methods

This US national longitudinal study assessed a cohort of patients aged 18-64 years who were Medicaid beneficiaries and experienced nonfatal opioid overdoses. The Medicaid dataset included years 2001-2007. Death record information was obtained from the National Death Index. The data analysis occurred from October 2017 to January 2018.

Crude mortality rates per 100,000 were determined in the first year after the nonfatal overdose. Standardized mortality rate ratios (SMR) were estimated for all-cause and selected cause-specific mortality standardized to the general population with respect to age, sex, and race/ethnicity.

Results

The primary cohort included 76,325 adults with 66736 person-years of follow up. There were 5194 deaths within the first year of a nonfatal overdose. The crude death rate was 778.3 per 10000 person-years, and all cause SMR was 24.2 (95% CI, 23.6-24.9). The most common immediate cause of deaths were substance abuse associated diseases (26.2%), diseases of the circulatory system (13.25%) and cancer (10.3%).  For every cause examined, SMRs were significantly elevated, especially with respect to drug use-associated diseases (SMR, 132.1; 95% CI, 125.6-140.0), HIV (SMR, 45.9; 95% CI, 39.5-53.0), chronic respiratory diseases (SMR, 41.1; 95% CI, 36.0-46.8), viral hepatitis (SMR, 30.6; 95% CI, 22.9-40.2), and suicide (SMR, 25.9; 95% CI, 22.6-29.6), particularly including suicide among females (SMR, 47.9; 95% CI, 39.8-52.3).

Conclusions

There was an elevated mortality in this US national cohort after a nonfatal opioid overdose due to a variety of causes including substance use-associated, mental health, and medical conditions. This underscores the importance of coordinating care between, substance abuse, mental health, and medical care of this population.

Clinical Commentary

This study highlights a piece that we in the mental health world may not be consciously aware off. This population of patients has poor general health, low immunity, lack of medical and self-care compounded with opioid abuse resulting in increased mortality. As a clinician I felt that after reading this article I should pay a lot greater attention to care coordination between mental health substance abuse and medical providers. We are often working in silos which may be mental health, substance abuse, or medical, and communication is vital and not happening. I would also underscore the importance of having the patient attend one program where all the care is under one roof rather than different agencies.

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Association of hormonal contraception with suicide attempts and suicides.

Skovlund CV et al. Am J Psychiatry. 2018 April1; 175(4):336-342. doi: 10.1176/aapi.ajp.2017.17060616. Epub 2017 Nov 17. PMID: 29145752

Background

Women in teenage years and young adulthood are prone to mood disorders. Hormonal contraception is commonly used worldwide. Relationship between depression and hormonal contraception is supported by research but little is known about suicidal attempts and completed suicide in this group of women. This study assessed the associations between hormonal contraception and suicide attempts and completed suicides in Denmark.

Methods

This longitudinal study extended from 1996 to 2013, was nationwide and prospective in nature. The cohort included women who had no previous psychiatric diagnoses, antidepressant use, or hormonal contraception use before age 15 years. Nationwide registers provided updated information about hormonal contraception use, suicide attempt, suicide, and confounding variables. The risk of suicide and suicide attempt were estimated and compared between users of hormonal contraception and nonusers.

Results

The study followed approximately half a million women for an average of 8.3 years with a mean age of 21 years. During the study 6999 first suicide attempts and 71 suicides were identified. Compared with women who never use hormonal contraceptives the relative risk amongst current and recent users was 1.97 (95% CI=1.85-2.10) for suicide attempt, and 3.08 (95% CI=1.34-7-08) for suicide. Risk estimates were higher for oral progestin-only products and highest for the vaginal ring. The association between contraception use and first suicide attempts peaked after two months of use.

Conclusions

Hormonal contraceptives were positively associated with subsequent suicide attempt and suicide. The relative risk was highest in adolescent women.

Clinical Commentary

With the knowledge of mood disorder association with hormonal contraceptives and these findings about suicide attempts and completed suicides it is important for both the psychiatric practioner as well as primary care physician and OBGYN to screen the patient on hormonal contraception for mood disorder and death wishes. The assessment of suicidal risk is a part of mine and all mental health providers daily work. The findings of this study should be kept in mind when assessing risk especially in teenage women and especially in the first couple of months after being placed on hormonal contraception.

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Metabolic effects of antipsychotics on adiposity and insulin sensitivity in youths: A randomized clinical trial.

Nicol GE et al. JAMA Psychiatry. 2018 June13; 75(8):788-796. doi: 10.1001/jamapsychiatry.2018.1088. [Epub ahead of print] Nov 28. PMID: 29898210

Background

There is an increasing use of antipsychotics off-label in the children and adolescents to treat nonpsychotic behavioral disorders. There is an increased risk of related metabolic disorders in this age group. This prospective study was planned to assess the metabolic effects of antipsychotics on adiposity and insulin sensitivity in this population.

Methods

The trial recruited antipsychotic naïve youth (N=144) between age 6-18 years in the St Louis, Missouri metropolitan area with psychiatric disorders who had significant aggression in which antipsychotic treatment was considered. Enrollment was between June 2006 and November 2010. The subjects were randomized (1:1:1) to one of three antipsychotics commonly used in the clinical setting and followed for 12 weeks. The antipsychotics included oral aripiprazole (N=49), olanzapine (N=46), or risperidone (N=49)

The primary outcomes included percentage total body fat measured by dual-energy x-ray absorptiometry (DXA) and insulin sensitivity in muscle measure via hyperinsluinemic clamps with stable isotopically labelled tracers. The secondary outcomes included abdominal adiposity measured by MRI and adipose and hepatic tissue insulin sensitivity measured by clamps and tracers.

Results

The sample included 68.1% males and 51.4% were of African American descent. Baseline obesity was observed in 29.9% of the sample. In 12 weeks the DXA percentage total body fat increased 1.18% for risperidone, 4.12 % for olanzapine and 1.66% for aripiprazole. The increase was significantly greater for olanzapine than risperidone or aripiprazole (P<.001).  The insulin sensitivity decreased significantly during 12 weeks in the pooled study sample (effect of time, F=17.38; P<.001). MRI measures of abdominal fat were significantly increased for olanzapine compared to risperidone or aripiprazole (time by treatment, P=.003). Behavioral improvements occurred with all treatments.

Conclusions

Increased adiposity and decreased insulin sensitivity were observed during 12 weeks treatment in youth with greatest fat increases in the olanzapine group. These changes increase the cardiometabolic risk.

Clinical Commentary

The clinical lore and open label data suggested increased weight gain in children and adolescents prescribed atypical antipsychotics. These drugs are being increasingly used off label in this population and this use has also come under scrutiny. This prospective study serves as an objective guide. Olanzapine should not be a first line drug, though we all know it is highly efficacious at controlling symptoms. Risperidone and aripiprazole are better choices, though with risperidone one needs to be aware of elevated prolactin and its risks of galactorrhea and aberrant menstrual cycle. With aripiprazole we need to monitor for akathisia. In the case of aripiprazole prolactin elevation is a nonissue. The multiple ramifications of increased adiposity both physically and psychologically suggest we try either risperidone or aripiprazole first and be judicious about it. It is worth noting that 30% of the sample was obese at baseline. Hence, it is all the more important to minimize weight when selecting an antipsychotic.

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Prospective longitudinal study of predictors of postpartum-onset depression in women with a history of major depressive disorder.

Suri R et al. J Clin Psychiatry. 2017 Sep/Oct 29.pii; 16r10732. 78 (8):1110-1116. doi: 10.4088/JCP.15m1042 PMID: 28297589

Background

Women with a history of major depression are vulnerable to postpartum depression. This study evaluated risk factors for postpartum depression in euthymic pregnant women with a history of major depressive disorder.

Methods

343 pregnant women with a history of major depressive disorder by Structured Clinical Interview (SCID) for DSM-IV were assessed prospectively from the third trimester into the postpartum period. The assessments included the SCID mood module and the 17-item Hamilton Depression Rating Scale (HDRS). Data from 300 subjects who completed at least two mood module assessments (one within 60 days before and the other within 60 days after delivery), was analyzed for predictive associations between variables assessed in the third trimester and the development of a postpartum depression. The recruitment period was from April 2003, to March 2009.

Results

The majority of subjects were euthymic in pregnancy. Women with third trimester SCID diagnosed depression (N=43) versus euthymia (N=255) had a significantly higher risk for having depression after delivery (24% vs 11% p=.013). For pregnant euthymic women, third trimester total HDRS scores significantly predicted postpartum depression (p< .0001); specifically, 3 HDRS items were work activities, early insomnia, and suicidality. Antidepressant use in the third trimester did not protect against postpartum depression.

Conclusions

Amongst women with a history of MDD who are euthymic in the third trimester 3 HDRS items: work activities, suicidality, and early insomnia predicted postpartum depression. These items may be useful questions for clinicians to screen pregnant women with history of MDD for postpartum depression. It is also important to note that antidepressants in the third trimester do not confer protection against postpartum depression.

Clinical Commentary

This is the largest prospective study exploring risk factors for postpartum depression which can become a severe illness if untreated and can lead to psychosis and possible thoughts of harming the child. It interferes with bonding, care of the child and also affects the child.  Risk factors such as trouble with work, suicidal thoughts and early insomnia in women with a pervious history of MDD can be useful screening questions. It is important to note that 11% of women euthymic in pregnancy can develop postpartum depression which is equal to the rate of depression at any other time in women’s life. These three items are more reliable predictors of depression compared to the total HRDS Score which has somatic items which may be elevated in pregnancy and misleading. These three items may be an effective tool for screening for this disease for primary care, psychiatrists, and obstetricians. Finally, postpartum depression is also a predictor of bipolar disorder.

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Antisuicidal response following ketamine infusion is associated with decreased nighttime wakefulness in major depressive disorder and bipolar disorder

Vande Voort J L et al. J Clin Psychiatry. 2017 Sep/Oct 29.pii; 16r10732. 78 (8):1068-1074. doi: 10.4088/JCP. 15m10440 PMID:27929610

Background

Insomnia and disrupted sleep are associated with increased suicide risk. Ketamine has been associated with reduced suicidal thoughts. This study sought to evaluate differences in nocturnal wakefulness in depressed individuals who did and did not have an antisuicidal response to ketamine.

Methods

The study included 34 subjects with major depression (N=23) and bipolar depression (n=11) with baseline suicidal ideation, recruited between the years 2006 and 2013. The subjects completed a nighttime electroencephalography (EEG) the night before and after a single ketamine infusion (0.5 mg/kg over 40 minutes). There was also a heathy control group (N=22). Suicidal ideation was assessed at baseline and the morning after the infusion using the suicide item on depression rating scales, as well as the Scale for suicidal ideation. The nocturnal wakefulness was compared between those who had an antisuicidal response to ketamine and those who did not as well as the control group.

Results

The subjects with an antisuicidal response to ketamine showed significantly reduced nocturnal wakefulness the night after the ketamine infusion compared to those without an antisuicidal response (F1,22=5.04, P=.04). The level of nocturnal wakefulness after antisuicidal response to ketamine did not differ from nocturnal wakefulness in the control group (F 1,40=3.15, P=.08)

Conclusions

Reductions in wakefulness following ketamine may point to a biological mechanism underlying the effect of ketamine on suicidal ideation.

Clinical Commentary

These findings have important clinical implications. Intravenous ketamine has been shown to rapidly relieve depression, as well as suicidal ideation, which clinicians and patients struggle with. Predictors of response are still being developed as this non-FDA approved (off-label) treatment gains momentum. Reduced nocturnal wakefulness may be one such marker pointing to a biological mechanism for effect of ketamine on suicidal ideation as well as help predict the responders.

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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]

To contact GME, email us at [email protected]


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