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found that a combinational pharmacogenetic test was a better predictor of medication blood level and patient outcomes than single-gene testing alone.

Common psychiatric medications for depression and anxiety can react with patients’ genes in ways that inhibit the drugs’ effectiveness. It is possible to test single genes for potential interactions, but Myriad Genetics has developed a test that 

 The study found that testing variations in multiple genes led to better, more predictive results.

The study’s lead author was Anthony J. Rothschild, MD, Irving S. and Betty Brudnick Endowed Chair and Professor of Psychiatry at the University of Massachusetts Medical School. In the article, he and his coauthors explained the importance of the findings as follows: “This evaluation of clinical validity shows that only the combinational pharmacogenomic test was significantly associated with improved patient outcomes. In addition, the combinatorial pharmacogenomic test was a superior predictor of medication blood levels across a larger group of medications relative to guidelines focused on only CYP2C19 and CYP2D6.”

The study was based on data from the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial.

 Between 2014 and 2017, the GUIDED trial drew participants from 60 psychiatry and primary care centers around the United States. In order to be eligible, participants needed a major depression disorder diagnosis and a score of 11 or more on the 16-item Quick Inventory of Depressive Symptomatology Scale at screening. They also needed at least 1 failed trial of psychotropic medication during their current depressive episodes.

 Participants were placed blindly into the pharmacogenomic-guided care or conventional treatment arms of the trial for 8 weeks. The researchers then measured and analyzed their outcomes.

The GUIDED trial did have some limitations. It was not a controlled pharmacokinetics study, meaning “blood levels were not controlled for time of intake or medication adherence.”

 As blood levels were only collected at screening, they could not be directly linked to adverse events or other outcomes. Still, the results were promising.

“This analysis demonstrates that the combinatorial approach of the GeneSight test more accurately predicts blood drug levels and identifies more patients with significant gene-drug interactions who would be missed by single-gene testing,” Mark Pollack, MD, chief medical officer of Myriad Neuroscience, said in a statement to the press. “Combinatorial pharmacogenomics like the GeneSight test should become the standard-of-care to help physicians understand gene-drug interactions that could improve care for people with depression, anxiety and other conditions.”

1. Rothschild AJ, Parikh SV, Hain D, et al. Clinical validation of combinatorial pharmacogenomic testing and single-gene guidelines in predicting psychotropic medication blood levels and clinical outcomes in patients with depression. 

2. GeneSight psychotropic test’s combinational approach proves better than single-gene testing at predicting patient outcomes and medication blood levels. 

February 8, 2021. Accessed March 4, 2021. 

https://www.globenewswire.com/news-release/2021/02/08/2171246/0/en/GeneSight-Psychotropic-Test-s-Combinatorial-Approach-Proves-Better-than-Single-Gene-Testing-at-Predicting-Patient-Outcomes-and-Medication-Blood-Levels.html

A study finds that testing genetic variations can predict outcomes and medication blood levels in patients with depression. 

How Will Patients React to Medications? The Answer May Be in Their Genes

A phase 2 trial of an adjunctive treatment for schizophrenia has stopped after failing to meet its primary and secondary endpoints. The treatment, CTP-692, developed by Concert Pharmaceuticals Inc, was a deuterated form of D-serine.

“The body of evidence in the field supporting D-serine as an adjunctive treatment for schizophrenia was compelling and led us to advance CTP-692 into a Phase 2 proof of concept study,” Roger Tung, PhD, president and chief executive officer of Concert Pharmaceuticals 

. “Unfortunately, we didn’t see the results we hoped for to support continuation of this program.”

CTP-692 was designed to improve on the efficacy and safety profile of existing schizophrenia treatments. Current research suggests that D-serine can improve outcomes for patients with schizophrenia, but it is accompanied by significant 

 Patients with schizophrenia also experience from cognitive impairments, and it was hoped that D-serine, which has shown positive effects on cognition in other contexts, would improve patient cognition without the renal risks.

The phase 2 trial was a double-blind, placebo-controlled study. It included 325 patients on antipsychotic medication. These participants were randomly selected to receive 1, 2, or 4-gram doses of CTP-692 once-daily, or a placebo. The trial took place over a 12-week period.

At the end of the 12-week period, the patients showed no improvement on the Positive and Negative Syndrome Scale (PANSS) compared to baseline scores, and the trial was discontinued. The company has also decided to discontinue study of this compound.

1. Concert Pharmaceuticals announces results from CTP-692 phase 2 trail in patients with schizophrenia. News release. Concert Pharmaceuticals Inc. February 1, 2021. Accessed February 17, 2021. 

https://ir.concertpharma.com/news-releases/news-release-details/concert-pharmaceuticals-announces-results-ctp-692-phase-2-trial

2. Concert Pharmaceuticals discontinues schizophrenia drug after trial failure. GlobalData Healthcare. February 3, 2021. February 17, 2021. 

https://www.clinicaltrialsarena.com/comment/concert-pharmaceuticals-schizophrenia-failure/

Is this phase 2 trial the end of the road for a potential new treatment?

A Potential Schizophrenia Treatment Trial Falls Short 

Previous systematic reviews estimate the 

 of attention-deficit/hyperactivity disorder (ADHD) worldwide as 5.6% to 7.2%.

 that some ethnocultural groups, such as Black individuals, are underrepresented in studies.

 found a higher prevalence of ADHD in Black than white youth, with evidence for a wide range in individual estimates for Black youth.

 Many factors may contribute to this variability.

 conducted a systematic review and meta-analysis to determine the pooled prevalence estimate of ADHD and associated individual, familial, and social factors among Black individuals, toward evidence-based and culturally adapted programs. The authors search PsychInfo, MEDLINE, Embase, Cochrane CENTRAL, CINAHL, ERIC, and Education Source from inception through October 2019. The search was designed by considering previous systematic review search strategies focused on Black participants. The authors included journal articles published in English or French with empirical data on the prevalence of ADHD samples in Black individuals in countries where they are considered a minority population (eg, United States and Canada).

The authors screened 3833 articles by title/abstract, from which they assessed 99 full-text articles for eligibility. Twenty articles met the inclusion criteria, and an additional article was found by manually searching the reference lists of these articles (

). Thus, 21 studies (24 independent samples), including 2 samples of adults, were included in the meta-analysis, all of which came from the United States.Each study was subjected to a quality assessment. Random effects meta-analysis on the proportion of 

The included studies had a combined sample size of 154,818. The pooled prevalence of ADHD was 14.5% (95% CI 10.6%-19.6%), with significant between-study heterogeneity. There was no evidence of publication bias based on a funnel plot and Kendall τ rank-order correlation. A similar pooled prevalence of 13.9% was found after excluding the 2 adult samples. Although some individual studies found sociodemographic (eg, age, sex, socioeconomic status), familial, and environmental risk factors, and risk behaviors, there were inadequate data to perform a moderation analysis, so a narrative review was performed. Some replicated risk factors (reported in 3 or more studies) include male sex, Black (versus other) race, low socioeconomic status, and 

or childhood exposure to toxic substances. The authors conducted the first meta-analysis of the prevalence and risk factors associated with ADHD in Black individuals in the United States. The 14.5% prevalence of ADHD in this population is greater than estimates from previous systematic reviews, suggesting a higher prevalence of ADHD in Black individuals.

 is a risk factor for ADHD in Black individuals, high socioeconomic status is not a protective factor. The authors noted that findings highlight the need for studies on associations between race and race-associated experiences and the diagnosis, prevalence, and risk factors associated with ADHD. Research on ADHD in other non-US Western countries should take ethnicity into account, and the absence of data from these countries is a limitation of the present study.Another limitation was the absence of inadequate data to quantitatively investigate potential moderating factors (eg, age, sex).

Findings from this meta-analysis challenge the notion that Black individuals have a lower prevalence of ADHD than other races. More research is needed to establish accurate diagnoses and culturally appropriate care for Black youth with ADHD.

is professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for 

The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Stanley Medical Research Institute.

1. Polanczyk G, de Lima MS, Horta BL, et al. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. 

Prevalence of attention-deficit/ hyperactivity disorder

Attention deficit hyperactivity disorder in African American children: what can be concluded from the past ten years?

From under-diagnoses to over-representation: black children, ADHD, and the school-to-prison pipeline

5. Cenat JM, Blais-Rochette C, Morse C, et al. 

Prevalence and risk factors associated with a ttention-deficity/hyperactivity disorder among US black individuals: a systematic review and meta-analysis

Diagnostic and Statistical Manual of Mental Disorders, 5th edition

 Arlington, VA; American Psychiatric Association: 2013.

Research on the prevalence of ADHD in Black individuals in the United States highlights the need for future research in this underrepresented group.









Busting Myths About Black Individuals With ADHD

Fabry disease is a rare genetic disorder, so rare that its psychiatric consequences remain poorly understood. Although there have been studies evaluating psychological and psychiatric issues among patients with Fabry disease, very little has been written about individuals challenged by the burdensome symptoms associated with the disease, or about the emotional distress that can result from living with a 

. It is crucial that health care providers are equipped to recognize potential psychological or psychiatric challenges and are able to refer patients with Fabry disease for an appropriate assessment. A better understanding of anxiety and depression in Fabry patients has important implications for health service planning, evaluation of therapeutic treatments, and clinical management.

Fabry disease is a pan-ethnic, X-linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A (α-GAL); that results in the progressive accumulation of globotriaosylceramide, or Gb3.

 Classic Fabry disease mutations are seen in approximately 1:22,000 to 1:40,000 males, and atypical presentations are associated with about 1:1000 to 1:3000 males and 1:6000 to 1:40,000 females with a spectrum of phenotypes.

 Phenotypes vary from the classic phenotype, to a later-onset, predominantly cardiac phenotype. Manifestations are diverse in female patients in part due to variations in residual enzyme activity and X chromosome inactivation patterns. Newborn screening (NBS) studies revealed frequencies of the classic and later-onset phenotypes of up to 1 in 22,570 males and 1 in 1390 males, respectively.

As Fabry disease progresses, it results in a multisystemic disease affecting the renal, cardiac, pulmonary, ocular, and dermal systems, as well as the peripheral and central nervous systems (CNS).

 Consequently, as substrate continues to build up, cellular dysfunction triggers organ impairment and eventually system damages. This can lead to substantial morbidity and 

, especially for patients who are untreated.

Fabry disease encompasses a spectrum of phenotypes ranging from the severe classic phenotype to atypical forms. The effective management of Fabry disease requires a multidisciplinary approach. It can be treated with bimonthly infusions of enzyme replacement therapy (ERT) to replace deficient α-galactosidase A, oral chaperone therapy, conventional medical treatment, or adjunct therapies.

CNS involvement precipitates cerebral micro and macro angiopathy leading to 

 at an early age, with an estimated prevalence of 6.9% in male and 4.3% in female Fabry disease patients.

 CNS alterations reported include increased occurrence of white matter lesions (WML), dilation and tortuosity of the larger intracranial arteries, signal enhancement of the lateral pulvinar on T1 weighted images, and hippocampal atrophy.

 In non-Fabry cohorts, WMLs have frequently been related to processing speed, memory, and executive functioning deficits.

 In Fabry disease, cognitive deficits have been described primarily in attention, executive functions, and psychomotor performance.

Autopsy studies in Fabry disease patients have repeatedly shown severe globotriosylceramide (Gb3) accumulation in the neurons and ganglion cells of the hippocampus, which could ultimately lead to functional deterioration of the cells, compromised energy metabolism, oxidative stress, and cellular death.

 Gb3 deposition in Fabry disease is the result of the inherited reduction of α-Galactosidase and causes clinical manifestation in early childhood, with a slight delay in girls.

 Early accumulation of Gb3 in the lysosomes of cells and subsequent cellular death could thus be responsible for such early hippocampal atrophy, as observed in some studies. Neuropathic pain and major depression have also been shown to be strongly related to reduced hippocampal volume (HV) in otherwise healthy subjects.

 Given that pain and depression are frequent symptoms in Fabry disease, the impact of both on HV decline seems expected, but research is variable. Depressive symptoms naturally fluctuate over the course of time due to symptom variability and progression of the disease.

 Placebo-controlled studies are needed to address antidepressant treatment options in patients with Fabry disease, as 

 can be a major burden on the lives of patients and families.

In Fabry disease, the presence of substrate accumulation can be traced back to the prenatal period; however, symptoms generally do not develop before early childhood.

 Affected children may experience acute and chronic neuropathic pain, described as a burning sensation and tingling in the hands and feet (acroparesthesia). They may also present with sweating abnormalities (anhidrosis, hypohidrosis) that make it difficult to exercise and perform physical activities. Abdominal pain and diarrhea have also been reported. During adolescence, gastrointestinal problems may increase in severity and frequency, and proteinuria can become elevated. Fabry crisis, manifested as severe pain radiating from the hands and feet, may occur spontaneously as a response to various environmental conditions like heat, cold, 

, and fatigue. Swelling of the affected areas (lymphedema) and redness may also be present and are predictors of future heart and renal dysfunctions. Vascular skin lesions (angiokeratomas) can appear, clustering around the umbilicus and swim trunk areas. With advancing age, patients may present with respiratory problems, cardiac and cerebrovascular manifestations, and 

 or tinnitus. Late disease is characterized by life-threatening renal failure, stroke, and severe cardiac problems.

Depression is common and underdiagnosed in Fabry disease. Previous research found that 60% of the patients enrolled in a study presented with clinical depression compared to healthy controls.

 Overall, depression is by far the most frequently reported psychiatric complication of Fabry disease, ranging from 15% to 62.5% in all series. Despite its prevalence, depression is not often discussed at clinic visits (

). Although depression and anxiety are often reported, referrals to psychologists or psychiatrists are limited, and mental health professionals are rarely involved as part of the care team.

Studies past and present have indicated that depressive symptoms in Fabry disease can be related to pain as well as social factors, including economic status.

 Conversely, the relationship between depressive symptoms and renal, cardiac, or cerebral involvement is generally less prominent; subjective health perception plays a more active role.

Differences in coping might influence the psychological well-being of Fabry patients. In a recent study, it was found that coping styles that involve avoiding emotional distress led to more depressive symptoms, while positivity and problem solving led to less depressive symptoms.

 Given the chronic multisystemic manifestations—pain, lack of sleep, and crippling fatigue—it would be extraordinary if individuals living with Fabry disease did not have to manage any psychological challenges.

Determining the importance of different factors related to depressive symptoms can aid in the identification of patients at risk and act as a starting point for specific psychological interventions to prevent or treat depressive symptoms.

Importance of Psychological and Psychiatric Evaluation

Over the past 20 years of working with patients diagnosed with Fabry disease, it has been troubling to see that common themes of depression, 

, uncertainty, and frustration are often reported before interventions for psychological difficulties are considered. In my practice, it is apparent that many individuals living with chronic conditions find it difficult to advocate for themselves. During an appointment, patients may report that they are exhausted, misunderstood, or cannot face being judged if they mention that they experience depression or anxiety. Patients often worry that telling their health care provider that they are depressed or anxious may require an additional appointment, causing them to feel overburdened. This discouragement can result in feelings of self-doubt, anger, and fear that serve to worsen depression. Also, depression associated with a chronic medical illness often aggravates the condition, especially if the illness causes pain and fatigue, or limits the ability to interact with others.

It is critical that patients with Fabry disease have the support and resources they need to understand the physical manifestations and the psychological challenges that the condition can cause. Building a broader understanding of these issues can improve quality of life, as patients no longer have to define themselves by their illness. Learning how to process and explore these issues can provide a normalizing and gratifying opportunity to be happier and enjoy more success.

There are many steps a care team can take to screen for psychological issues. Primary care encounters are often the only opportunities for patients with Fabry disease to address emotional challenges and obtain the professional attention they require. For clinicians, forging empathetic partnerships with patients, prescribing appropriate treatments, and closely monitoring symptoms and therapeutic progress are invaluable for optimal management of both affective and medical disorders.

Cognitive behavioral therapy is often considered the most effective therapy for depression and anxiety. If patients are continuously thinking about negative outcomes, they begin to have a generalized feeling of hopelessness that can lead to a depressed or anxious mood. It can be beneficial for health care providers to help patients with Fabry explore ways to manage the disease. The common approach is to challenge negative thoughts and prompt the patient to explain the basis of their negative health perceptions.

Behavioral activation is just as important as the cognitive components of therapy. To help improve mood, patients should be encouraged to set goals and regularly partake in activities that they enjoy. In addition, many patients with depression and anxiety feel empowered when they can help choose the treatment approach used to manage their disease. Having a role in deciding how treatment is approached can also help support adherence, which is critical when coping with severe symptoms.

While data on the impact of depression treatment for patients with Fabry disease are limited, a recent pilot study examined the effects of psychological counseling on depression, adaptive functioning (AF), quality of life (QOL), and subjective pain experience. Subjects completed 6 months of in-person or telecounseling with the same health psychologist, followed by 6 months without counseling. Self-report measures of depression, AF, QOL, and subjective pain were completed every 3 months. All subjects experienced improvements in depression, which were sustained during the follow-up period.

 Study findings support the efficacy of psychological treatment for depression in individuals with Fabry disease, with additional benefits achieved when health psychologists aligned closely with lysosomal storage disease treatment centers in the patient management continuum.

Patients with depression and chronic illnesses such as Fabry disease are challenging to treat, but they are exactly the type of patient that can benefit from expert care.

 A growing body of evidence supports the view that chronic medical conditions and depression are interrelated. Collaborative care for psychological challenges is a treatment model that uses a multimodal, biopsychosocial, structured, evidence-based approach, involving nonmedical specialists. It is critical that care teams work with patients to develop a shared definition of potential issues, provide education and support, target treatment goals, develop a specific treatment plan, and provide follow-up.

is a pediatric neuropsychologist with specialized training and expertise in rare genetic and neurodegenerative diseases. She served as faculty at the University of Minnesota and at the University of Colorado-Denver/Children’s Hospital Colorado where she participated in the neurometabolic, neurogenetic and neuromuscular clinic care teams. Dr Bjoraker is known nationally and internationally for her expertise in lysosomal storage diseases and other inborn errors of metabolism and neurodegenerative diseases. She is a presenter and researcher with extended publications in rare genetic diseases and experience in clinical trial development. Dr Bjoraker is also a consultant in Minneapolis, Minnesota.

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A rare genetic disorder may have unrecognized psychological consequences. 

Don’t Forget About Fabry Disease  

A new test screens for bipolar disorder with respectable accuracy

How to Screen for Bipolar Disorder in 2 Minutes

An article in the December 2020 issue, “

The Intertwining Effect of Mood Disorders and Infertility

,” made many important points. I would like to raise to a few additional issues that seem to be often overlooked.

Women taking serotonin uptake inhibitors (SSRIs) to help them cope with infertility are actually increasing their serum prolactin to an unhealthy level. This hyperprolactinemia, in turn, 

 Unknowingly, they are hindering their changes of conception. This is the biology underlying the common folk wisdom that one cannot usually become pregnant while lactating/breastfeeding. This is when prolactin levels are very high.

I urge all women with fertility issues, especially those on SSRIs, to get a simple blood test measuring their serum prolactin level. An elevated serum prolactin level can be corrected with oral dopamine agonists (dopamine-stimulating) medications.

Certain antipsychotic meds, whether typical or atypical, can also elevate serum prolactin levels. Risperidone in particular can cause hyperprolactinemia in female and males, which causes lactation (galactorrhea) from their breasts. A third, less common cause of hyperprolactinemia is a tumor of the anterior pituitary gland, known as an anterior pituitary adenoma. This can be detected by an MRI of the brain.

Once identified, hyperprolactinemia can be readily corrected by dopamine agonists such as 

 Once the prolactin level has come back down to the normal rage, ovulation can occur. The patient can then discuss with her psychiatrist whether or not to continue the psychotropic medications at the current doses or lower, depending on the severity of her particular symptoms and stressors.

In conclusion, women struggling to conceive who are on SSRIs and/or antipsychotic medication should request that their serum prolactin levels be checked. This cause of infertility can be readily corrected. Therefore, it should be checked, especially before moving on to more invasive and uncomfortable fertility tests, such as a hysterosalpingogram, and certainly before beginning the injections to prepare for IVF.

is a psychiatrist at the Manhattan Psychiatric Center, in the Outpatient Department on 125th St., NYC. She is the author of 

, forthcoming from Amazon, and played Dr Zalutsky on “The Sopranos.”

1. Torre DL, Falorni A. Pharmacological causes of hyperprolactinemia. 

2. Matsuzaki T, Azuma K, Irahara M, et al. Mechanism of anovulation in hyperprolactinemic amenorrhea determined by pulsatile gonadotropin-releasing hormone injection combined with human chorionic gonadotropin. 

3. Schlechte JA. Long-term management of prolactinomas. 

In addressing mood disorders associated with infertility, sometimes the cure may be worse than the disease. 

Do SSRIs Decrease Fertility?

Susan Noonan, MD, MPH, talks how small, broken down tasks and a system will help patients maintain their mental health. 

is a physician consultant and Certified Peer Specialist in the Department of Psychiatry at McLean Hospital and the Massachusetts General Hospital. She is the author of four books and a blog on managing depression, most recently 

Helping Others With Depression: Words to Say, Things to Do (December 2020)

. Dr Noonan offers peer counseling to fellow patients, including physicians and other professionals, and can be confidentially reached through her website at 

Daily routine and structure will decrease a patient's stress and give them a sense of accomplishment. 

Manageable and In Control 

According to Susan J. Noonan, MD, MPH, high nutrient-dense foods, like colorful fruits and vegetables, whole grains, beans, fish, poultry, and a small amount of olive oil and dairy can improve your patient's mood and lower their risk for depressive episodes. 

Keeping glucose levels steady may also help prevent mood swings. 

 is a physician consultant and Certified Peer Specialist in the Department of Psychiatry at McLean Hospital and the Massachusetts General Hospital. She is the author of four books and a blog on managing depression, most recently 

Helping Others With Depression: Words to Say, Things to Do

 (December 2020). Dr Noonan offers peer counseling to fellow patients, including physicians and other professionals, and can be confidentially reached through her website at 

A healthy diet can improve mood and effectiveness of antidepressant medications. Here's why your patients should be eating healthier. 

Food Is the Fuel

10 Salient Points About Migraine and Psychiatric Comorbidity 

Where do migraines and psychiatric disorders intersect? Learn more. 

Valproate/divalproex appears to be considerably overused in the US; the use of lithium, second-generation antipsychotics, and carbamazepine should be more prominent in treatment decisions for patients with bipolar mania.

Valproate/divalproex was approved by the FDA for use in bipolar mania with the publication of a major study in 1994 that showed efficacy. It was heavily marketed and entered the mainstream practice in the US. It has been used less in Europe and even less in Japan where carbamazepine is more popular as an alternative to lithium. In the 1970s, Japanese researcher Teruo Okuma, MD, PhD, was the first to demonstrate the effect of carbamazepine in mania.

As there have been more studies, the evidence base for the efficacy of this product has become less and less impressive. In the last 2 published placebo-controlled trials of divalproex in acute mania (1 in adults, 1 in adolescents and young adults), there were no differences from placebo; and, in the 

published just before those, the effects were statistically significant but quite small.

 Meta-analyses of controlled studies of medications for acute mania find it to have a 

 size than lithium, carbamazepine, and antipsychotics.

Maintenance trials have not shown efficacy, and the medication does not have FDA approval as a maintenance treatment for bipolar disorder. Its use for that purpose, although common, is off-label. Valproate/divalproex is also not approved for treatment of acute bipolar depression nor for prevention of depressive episodes. However, there are a few small studies that 

that it could work for bipolar depression; larger studies are needed.

One group of patients with bipolar disorder that seem to fare better on valproate includes those with acute mixed mania (ie, meeting full criteria for mania but having 3 or more symptoms of depression concomitantly). Valproate may be preferred over lithium for such patients.

Clinicians often choose valproate because of a perception that it has a milder adverse effect profile than other bipolar medications. However, head-to-head studies indicate that 1 very important adverse effect—weight gain—is greater with valproate than with lithium, olanzapine, and quetiapine.

 The risk of suicidal behaviors is twice as high on anticonvulsants such as valproate compared with controls, whereas substantial evidence finds reduced risk of suicidality on lithium. Liver dysfunction and, less commonly, pancreatitis, thrombocytopenia, and polycystic ovaries are other significant adverse effect issues with valproate. It has the most teratogenicity of any medication used in bipolar disorder and has been 

by experts to be a last resort medication for any woman of child-bearing potential.

In conclusion, valproate/divalproex appears to be considerably overused in the US. Clinicians should think of lithium, second-generation antipsychotics, and carbamazepine more prominently in selecting medication for patients with bipolar mania. Patients should be informed of the evidence-base for efficacy and FDA approval status before being prescribed valproate for acute illness and especially for maintenance usage.

 is Associate Professor of Psychiatry, Harvard Medical School, and Consulting Psychiatrist, US Department of Veterans Affairs, National Telemental Health Center, Bipolar Disorders Telehealth Program, Brockton, MA.

This article was posted ahead of print on June 16, 2020, under the title "Valproic Acid: Its Role in Bipolar Disorder," and has since been updated. -Ed

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Mood Disorders