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Issue 94, Feb 2020
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What you eat dictates how you feel: Dietary interventions in psychiatric patients

Fond G et al. J Affect Disord. 2019 Nov 14. Pii S0165-0327(19)31770-7.doi: 10.1016/j.jad.2019.11.092. [Epub ahead of print]

PMID:31757621

Background

There is an increased focus on nutrition and mental health resulting in an emerging field in psychiatry. This study was conducted to highlight recent findings in the field to guide nutritional interventions in psychiatry.

Methods

This Anglo-French study was a metanalysis of psycho nutrition studies in severe mental disorders.

Results

The Mediterranean diet had the best evidence for effectiveness in diminishing the incidence of depressive symptomatology. Complimentary agents were found to be associated with lower depression levels. The agents included omega 3 fatty acids, vitamin D, methylfolate, and S-adenosylmethionine which are all components of the Mediterranean diet. The Healthy Eating Index (HEI) has been associated with lower depression levels. Additionally, a diet with a low Dietary Inflammatory Index was found to be associated with lower depression. These effects may be mediated by microbiota modifications and probiotic supplementation. High protein diets have been shown to effective for weight loss and increasing satiety without deleterious effects in subjects without chronic conditions such as renal failure, diabetes, and cardiovascular disease. A reduction of 20% intake may also improve microbiota and hence psychiatric conditions.

Conclusions

In light of these findings, dietary modifications appear to be an underutilized tool with which to improve the mental and physical health of psychiatric patients.

Clinical Commentary

This study provides evidence for nutrition education in the treatment of mood disorders. In my opinion, there is consensus that the quality of food being consumed by a vast majority of individuals has changed from traditional home-cooked to processed fast food. The consumption of such foods may occur to a larger extent in the mentally ill populations. Living life in the fast lane has also added to this problem. The treatment of depression and other psychiatric disorders should be comprehensive to include medications, psychotherapy and lifestyle management. Nutrition and exercise are included as part of lifestyle management. Other factors that help are therapeutic massage, yoga, and meditation.

Major depression has been associated with inflammatory disturbances and diet with a low Dietary Inflammatory Index is associated with lower depression. These effects may be mediated by microbiota modifications.

DASH diet https://www.nhlbi.nih.gov This diet is helpful (rich in fruits and vegetables) in the prevention of hypertension. Besides, increased physical activity, and maintaining a healthy weight are important.

The Mediterranean diet is a heart and brain-healthy diet (https://www.mayoclinic.org). This diet tends to be more plant-based. It has reduced risk factors for cardiovascular disease and is also recognized by the World Health Organization (WHO). This diet plan includes the consumption of fruits, vegetables, whole grains, and healthy fats (olive oil, nuts, and seeds). Besides, it also includes intake of poultry, beans and eggs, and fish (herring, sardines, salmon, mackerel). Dairy (e.g. plain yogurt) is included and red meat intake limited.

MIND diet (The Mediterranean-DASH Intervention for Neurodegenerative Delay) https://www.todaysgeriatricmedicine.com. This diet is an offshoot of the Mediterranean and DASH diet and is good for brain health.

A diet plan that is easy to follow and not too rigorous, can be incorporated and can be pursued over an extended time frame. A significant cultural change needs to happen. Psychiatrists and other mental health providers can collaborate with trained nutritionists to implement a comprehensive treatment plan.

There are limitations of reviews and meta-analyses. These include the quality of studies chosen, heterogeneity of findings and a publication bias towards positive studies. We should be mindful of these issues when reviewing meta-analyses.

In summary: We clinicians should begin to incorporate the dietary aspect into our treatment plans. Community mental health clinics and PROS programs, intensive outpatient programs are well placed to add on the nutritional aspect. Currently, the Mediterranean diet has the most evidence. Collaboration with nutritionists might help with less expensive options as substitutes.

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Is running (jogging) associated with a lower risk of all-cause, cardiovascular and cancer mortality, and is the more the better? A systematic review of meta-analysis.

Pedisic Z et al. Br J Sports Med. 2019 Nov 4: Pii: bjsports-2018-100493. doi: 10.1136/bjsports-2018-100493. [Epub ahead of print]

PMID:31685526

Background

Running has been gaining in popularity with individuals training to do half-marathons and full marathons. Many cities now organize a yearly marathon. There are also other fundraiser runs during the year. There has been a revival of focus on health and nutrition recently. This study aimed to investigate the association of running participation and the dose of running with the risk of all-cause, cardiovascular and cancer mortality.

Methods

This study was multicultural involving Australian, Thai, and Finnish investigators. The information was obtained from multiple scientific databases, conference papers, and a doctoral thesis. The eligibility criteria included prospective cohort studies on the association between running or jogging participation and risk of all-cause, cardiovascular and/ or cancer mortality in a non-clinical adult population.

Results

There were N=14 studies from six prospective cohorts which included 232149 participants. During the 5.5-35 years, follow-up 25951 deaths were recorded. The analysis revealed that running was associated with 27%, 30%, and 23% lower risk of all-cause, cardiovascular, and cancer mortality respectively compared to no running. There was no significant dose-response relationship.

Conclusions

This study suggests that increased rates of participation in running regardless of dose would lead to substantial improvements in population health and longevity. Any amount of running, even once a week is better than no running. Higher doses may not necessarily have greater mortality benefits.

Clinical Commentary

This study provided important data towards lifestyle management which is part of a comprehensive treatment plan for those with psychiatric disorders.There are reports of sudden cardiovascular death but the benefits of running outweigh the risks. This study was prospective and had a long follow-up. This study also utilized rigorous methodology including contacting authors. The limitations include the exclusion of those with cancer or cardiovascular disease which prevents people from running and also increasing their mortality. The total number of studies was small and hence publication bias cannot be excluded.

This study also fits in with the WHO guidelines which recommend 150 mins/ week of moderate-intensity exercise or 75 min/ week of vigorous exercise.

In patients with schizophrenia and mood disorders, cardiovascular disease is the most common cause of mortality. These patients also have a higher prevalence of diabetes, obesity, dyslipidemia, and hypertension (metabolic syndrome). Increased physical activity/ running should be pushed as part of the treatment plan.

In summary: The evidence exists that running is beneficial towards the reduction of all-cause mortality, cardiovascular disease, and cancer suggesting we should be discussing these aspects as part of the treatment plan. I would suggest that we "get them moving" in a stepwise fashion. If there are doubts the primary care physician can be consulted for medical clearance.

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Treatment of major depressive disorder (MDD): Light therapy versus antidepressant drugs and the combination versus monotherapy.

Geoffroy PA. et al. Sleep Med Review. 2019 Sep 18;48:101213. doi: 10.1016/j.smrv.2019. 101213 [Epub ahead of print]

PMID:31600678

Background

Light therapy has been used to treat seasonal and non-seasonal depression and remains an underutilized treatment while antidepressants are the mainstay. This study was designed to study the efficacy of antidepressants versus light therapy as well as monotherapy versus combination therapy.

Methods

This study included randomized controlled trials that compared that directly compared light therapy (LT) and antidepressant drugs (AD) as well as their combination (LT+AD). The patients included those suffering from moderate to severe major depressive episodes.

Results

The study included 397 participants with a median treatment duration of five weeks (range 2-8 weeks). There were no statistically significant differences between LT +placebo and AD+ placebo in lowering depression scores. No potential publication biases were observed. There was clear superiority of the combination.

Conclusions

This study suggests that LT monotherapy and the combination can be used as a first-line treatment in seasonal and non-seasonal depression.

Clinical Commentary

This is an interesting study that suggests that the treatment of seasonal and nonseasonal depression can be started with LT and antidepressants can be added later. No difference was noted between either treatment and the combination therapy was noted to be better. The studies included methodological flaws, small sample sizes, and heterogeneity suggesting a moderate strength of evidence.

Light therapy may hasten the response in as little as one week. Hypomania was reported in one case. Patients with bipolar disorder need to also be on mood stabilizer therapy.

The antidepressants used in the studies were mostly SSRIs. One study used a tricyclic antidepressant and head a greater effect size.

There are relative contraindications to LT primarily ophthalmological disorders such as cataracts, retinopathies, glaucoma, and retinitis pigmentosa. Patients in such cases should be cleared by the ophthalmologist.

The underutilization of LT has also been due to insurance coverage issues. Larger lightboxes are currently recommended. Below are three such lightboxes

Sun Ray II (Sun Box Company) distance 23 inches

North Star 10,000 (Alaska Northern Lights) distance 24 inches

Day-Light Classic (Model DL930; Carex Health Brands) distance 12 inches

The manufacturer recommended distance is the distance between the surface of the lightbox and the patient's eyes. This may affect the cost. This information was obtained from https://simpleandpractical.com/light/. Simple and practical.com is a great subscription website to get daily tips by email for practical psychiatry related topics.

Recommended Book: "Winter Blues" Norman Rosenthal MD

In summary: I do think we should be using LT more in clinical practice. This can especially be used as an augmentation strategy as noted in this paper. Usually, it is used from September to April. An hour a day in the morning. I also suggest the book to patients.

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Lithium exposure during pregnancy and the postpartum period: Review of safety and efficacy outcomes

Fornaro M. et al. Am J Psychiatry. 2019; Oct 18:appiajp201919030228. doi:10.1176/appi.ajp.2019. 19030228. [Epub ahead of print]

PMID 31623458

Background

Lithium is a highly efficacious medication used to treat mood disorders. It also reduces suicide risk. There remains uncertainty regarding the use of lithium in women during the peripartum period. Lithium use during pregnancy has been associated with Ebstein's anomaly and other cardiac defects. These risks have been downgraded but the controversy of using Lithium in pregnancy is still prevalent. The authors of this meta-analysis aimed to provide a critical review of the evidence related to the efficacy and safety of lithium treatment during the peripartum period. The focus was on women with bipolar illness and their offspring.

Methods

The study investigators conducted a meta-analysis assessing case-control, cohort, and interventional studies reporting on the safety (primary outcome, any congenital anomaly) or efficacy (primary outcome, mood relapse prevention) of lithium treatment during pregnancy and postpartum period. The Newcastle-Ottawa Scale and the Cochrane risk of bias tools were used to assess the quality of available PubMed and Scopus records through October 2018.

Results

There was a total of 29 studies included (20 studies were of good quality, six were poor quality, two had high risk of bias, and one had questionable bias). Finally, 13 of the 29 studies could be included in the quantitative analysis.

Lithium prescribed during pregnancy was associated with higher odds of any congenital anomaly (the number needed to harm (NNH)=33). Results were similar for first-trimester exposure. The association was significant in the analysis of patients restricted to those with affective disorders (NNH=38). The unexposed general population had an NNH =22.

Most malformations were diagnosed by one year of age. The cardiac anomalies included atrial and atrioventricular septal defects and Ebstein's anomaly.

Lithium exposure was associated with an increased risk of cardiac anomalies (NNH=71) compared to unexposed (NNH=37). There was no difference between those with affective disorders. First-trimester exposure increased the risk of cardiac anomalies (NNH=71) compared with unexposed. It was increased in comparison to the general population and those unexposed to lithium with affective disorders (NNH=83).

Lithium was more effective than no lithium in preventing postpartum relapse (NNH=3). Mothers with serum lithium level <0.64 mEq/L and dosages < 600 mg/ day had more reactive newborns without an increased risk of cardiac malformations.

Conclusions

The risk associated with lithium exposure at any time during pregnancy is low, and the risk is higher for first-trimester or higher-dose exposure. Pregnancy in the case of bipolar disorder should be planned during symptom remission and lithium prescribed in the lowest dose range throughout the entire pregnancy, particularly during the first trimester and the days immediately preceding delivery. The aim would be to balance the safety and efficacy profile for the individual patient.

Clinical Commentary

This study indicates that lithium is effective in preventing relapse but there is an elevated risk of any congenital anomaly including cardiac malformations. There is a tradeoff and the harmful effects are reduced at lithium dosages under 600 mg/day. The harmful effects are increased substantially at dosages > 900 mg lithium per day.

Although the lithium risk has been downgraded by this study as well as others conducted by perinatal psychiatrists it is difficult to get patients and clinicians to continue lithium in the perinatal period. Once patients find out they are pregnant they do not want to be on lithium.

A discussion needs to be held with the parents to be and a risk-benefit analysis including the risk of relapse discussed. It is important to discuss the consequences of relapse. Psychological stability is important for the mother to care for the newborn. A psychologically stable mother will also be able to develop a good bond with the child.

I do suggest the website: womensmentalhealth.org (Harvard Medical School) to my patients to review and document this recommendation in the record. A great article to read on this issue referenced N Engl J Med. 2017 Jun 8; 376(23): 2245–2254.

In summary: Regarding lithium risk, we often think about the fetus but forget the mother whose mental health and psychological stability are extremely important. The mother needs to be stable to take care of the child and bond. In the midst of a relapse, serious problems arise and in the case of a psychotic relapse, there is a risk of infanticide. Hence stable patients should continue on lithium during the entire pregnancy using the lowest dose < 600 mg/ day with a level in the range of 0.6 Meq/L. Finally, consent has to be obtained from both parents if possible and documented. In addition, excellent care coordination needs to be done with the family physician and the obstetrician.

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Stress-related psychiatric disorders and increased risk of life-threatening infections: Swedish population-based sibling controlled cohort study

Song H et al. BMJ. 2019 Oct 23;367:15784 doi; 1136/bmj.15784.

PMID 31645334

Background

PTSD and other psychiatric disorders often have a hand in glove relationship with medical conditions. This has been noted with stroke, migraines, diabetes, cholesterol, and heart disease to name a few. This study was designed to assess the relationship between psychiatric illnesses and subsequent life-threatening infections.

Methods

This Swedish study is population and sibling matched cohort study. There were 144919 individuals with stress-related disorders (post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions) identified from 1987 to 2013 compared with 184612 healthy full siblings of individuals with a diagnosed stress-related disorder and 1449190 matched individuals without such a diagnosis from the general population.

The primary outcome measure: A first inpatient or outpatient visit with a primary diagnosis of severe infections with high mortality rates (i.e., sepsis, endocarditis, and meningitis or other central nervous system infections) from the Swedish National Patient Register. The cause of death from these infections or any infections of any origin was determined from the cause of death register. Hazard ratios were estimated for these life-threatening infections.

Results

The sample included 38% males and the average age of diagnosis of a stress-related disorder was 37 years During the mean eight-year follow-up the incidence of life-threatening infections was 2.9 individuals per 1000 person-years in individuals with a stress-related disorder. It was 1.7 in siblings without a diagnosis and 1.3 in matched individuals without a diagnosis. Compared with full siblings without a diagnosis of stress-related disorder, individuals with a diagnosis were at increased risk for life-threatening infections. The hazard ratio was 1.7 for any stress disorder and 1.9 for PTSD.

Stress-related disorders had a higher risk of all kinds of infections with the highest risk being for meningitis and endocarditis. The risk was increased in those with a younger age of diagnosis of the stress disorder and the presence of substance abuse. The risk was somewhat attenuated with early treatment with a selective serotonin reuptake inhibitor (SSRIs).

Conclusions

In the Swedish population, stress-related disorders were associated with a subsequent increase in life-threating infections. The study did control for familial background, as well as physical and psychiatric comorbidities.

Clinical Commentary

This study finds that having stress-related disorder especially associated with substance abuse increased the risk of serious infections most commonly meningitis and endocarditis. Early treatment of the mental illness with an SSRI was somewhat beneficial.

This study has a large sample size and 27 year follow up. It was a prospective study hence information was more accurate.

The limitations include multiple analyses. The Swedish outpatient register being set up in 2001 underestimating individuals with stress-related disorders. The diagnosis also kept changing over the years. Lack of information on behavioral issues such as smoking and alcohol use.

An important finding was that siblings without stress-related disorder had a much lower incidence of (1.7 compared with 2.9 individuals per 1000 person-years in sibling with psychiatric disorder) severe infections but yet elevated compared with age-matched individuals from the general population (1.3 per thousand person-years) who do not have stress-related disorder. This suggests a role of genetics needing further study.

Stress-related cortisol increase may increase susceptibility to infections however studies have produced mixed results. The focus has shifted to inflammation as a resistance of the glucocorticoid receptor increases the release of inflammatory cytokines.

In summary: This study highlighted an important clinical issue for me as a clinician. The primary take-home message is increased clinical awareness about this issue especially in those diagnosed with stress disorders at an early age. It is also important to follow the inflammation story due to its potential role in this stress infection relationship. Early intervention of stress-related disorders with SSRIs attenuates these risks.

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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]

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