Left Prefrontal Strokes Linked to Depression

man touching head

In a 2021 article in the journal Stroke, researcher Julian Klingbeil and colleagues reported that left, but not right, ventrolateral prefrontal stroke lesions were associated with increased risk of depression at six months post-stroke.

The study included 270 participants who had their first-ever stroke. Six months following their strokes, 19.6% of the participants had depression. Those who scored higher on a scale of depression and anxiety symptoms in the first month after their stroke were more likely to have depression six months after the stroke.

The researchers identified a cluster of locations for stroke lesions, mostly within the left ventrolateral prefrontal cortex, that they linked to depression symptoms six months post-stroke. Klingbeil and colleagues hope that recognizing lesions in this region as risk factors for depression will help with early diagnosis of depression among people who recently had a stroke.

Editor’s Note: Antidepressants have been shown to improve post-stroke recovery of neurological functional (and depression) that is caused by the cutoff of blood supply during a stroke (ischemia). Patients and their family members should talk with their neurologist about treatment of ischemic strokes with antidepressants, especially when the lesions occur on the left side of the brain.  

Psychiatric Disorders Linked to More Physical Disease

May 19, 2021 · Posted in Comorbidities, Peer-Reviewed Published Data · Comment 
man seeing primary care physician

In an article in the journal JAMA Network Open, Leah S. Richmond-Rakerd and colleagues found that people with mental disorders had more physical disease at younger ages, they had more and longer hospitalizations and associated health care costs, and they were more likely to die at younger ages than people without mental disorders.

The research came from a population-based cohort study of more than 2.3 million citizens of New Zealand over three decades. The authors concluded, “These findings suggest that ameliorating mental disorders may have implications for improving the length and quality of life and for reducing the health care costs associated with physical diseases.” 

Editor’s Note: This editor would suggest the importance of also doing the opposite, that is, looking out for and treating and preventing the physical illnesses to which psychiatric patients are more vulnerable in order to improve the length and quality of life.

Either way, medical illnesses, both physical and psychiatric, are intimately intertwined, and both deserve careful and early intervention. Psychiatric and physical illnesses cause suffering, disability, and early demise. Major psychiatric illnesses need to be seen as potentially lethal medical illnesses, a fact that few people realize. Conversely, physical illnesses are often not treated as aggressively or intensively in psychiatric patients as in the general population. For example, patients with bipolar disorder get fewer interventions with stents and bypasses for the same heart problems as others. Special attention needs to be given to better encourage and support the medical health of psychiatric patients.

ADHD Common in People with Mood Disorders

May 11, 2021 · Posted in Comorbidities, Diagnosis, Peer-Reviewed Published Data · Comment 
teenagers

In a meta-analysis published in the journal Acta Psychiatrica Scandinavica in 2021, researcher Andrea Sandstrom and colleagues reported that people with mood disorders had a three times higher incidence of attention-deficit hyperactivity disorder (ADHD) than people without mood disorders. ADHD was also more likely to occur in people with bipolar disorder than in people with major depression. The comorbidity is most common in childhood, less so in adolescence, and lowest in adulthood. 

Based on 92 studies including a total of 17,089 individuals, the prevalence of ADHD in people with bipolar disorder is 73% in childhood, 43% in adolescence, and 17% in adulthood. Data from 52 studies with 16,897 individuals indicated that prevalence of ADHD in major depressive disorder is 28% in childhood, 17% in adolescence, and 7% in adulthood.

Editor’s Note: A key implication of this research is that there is a huge overlap of bipolar disorder and ADHD in childhood, and that physicians need to specifically look for bipolar symptoms that are not common in ADHD to make a correct diagnosis. These include: brief or extended periods of mood elevation and decreased need for sleep in the youngest children; suicidal or homicidal thoughts and threats in slightly older children; hyper-sexual interests and actions; and hallucinations and delusions. When these are present, even when there are also clear-cut ADHD symptoms, a clinician must consider a diagnosis of bipolar disorder and treat the child with mood stabilizers prior to using stimulants or other traditional ADHD medications.

Conversely, physicians should be aware of the much lower incidence of ADHD in adolescents and adults with bipolar disorder. Here one should first make sure that the apparent ADHD symptoms of hyperactivity, inattention, poor concentration, etc. do not result from inadequately treated mania and depression, and if they do, treat these symptoms to remission prior to using traditional ADHD medications.

Study Examines Comorbidity of ADHD and Bipolar Disorder

three generations of men

In a 2021 review and meta-analysis in the journal Neuroscience and Biobehavioral Reviews, researcher Carmen Schiweck and colleagues described the comorbidity of attention-deficit hyperactivity disorder (ADHD) and bipolar disorder in adults. This was the first review and meta-analysis to quantify the comorbidity of the two fairly prevalent disorders. The meta-analysis included 71 studies with a combined total of 646,766 participants from 18 countries.

The review found that among people with ADHD, about 1 in 13 also have bipolar disorder, while among people with bipolar disorder, 1 in 6 have comorbid ADHD. The prevalence differed depending on the continent where patients lived and the diagnostic systems used there, with greater prevalence of both disorders in the US, where the Diagnostic and Statistical Manual of Mental Disorders is used, than in Europe, where the International Classification of Diseases is typically used. (Other parts of the world were less represented in the meta-analysis.) Schiweck and colleagues found that bipolar disorder had an onset about 4 years earlier in patients who had comorbid ADHD.

Insomnia Plays Critical Role in Bipolar Disorder

April 6, 2021 · Posted in Peer-Reviewed Published Data, Risk Factors · Comment 
man awake in bed

In a 2021 article in the Journal of Psychiatric Research, researcher Laura Palagini and colleagues reported that insomnia symptoms can affect the course of bipolar illness. In a helpful summary and interview in the Psychiatry & Behavioral Health Learning Network’s Psych Focus, she stated that: 

“1) BD patients in a depressive phase with clinically significant insomnia met a greater severity not only of depressive symptoms and suicidal risk, but also of early life stressors and the cognitive part of hopelessness, compared with patients without insomnia

“2) insomnia symptoms could predict mood symptoms, suicidal ideation and plans, and the cognitive component of hopelessness

“3) insomnia symptoms might mediate the effect of early life stressors on mood symptoms, hopelessness, and suicidal ideation and behaviors.”

Palagini suggested that “Insomnia symptoms should be easily addressed in clinical practice with 1–2 questions. Insomnia treatment should be considered as a treatment to prevent …relapse and recurrence [of bipolar disorder] and to prevent suicide and the effect of early life stress on [bipolar disorder].”

Editor’s Note:  Regular nightly rating of mood, functioning, hours of sleep, medications, life events, side effects, and other comorbid symptoms on the Monthly Mood Chart Personal Calendar (pdf) is an easy way for patients with bipolar disorder to carefully track their illness trajectory and the completeness of their response to medications.

A decrease in the hours of sleep should be used as a possible early warning sign of impending difficulties, or even a new episode. Patients should discuss with their physician the threshold of insomnia (such as the loss of 2 hours of sleep for two days in a row) that should trigger a call to the physician, and what interventions the patient might initiate for lesser amounts of sleep loss and/or changes in mood. Heading these off early may prevent the breakthrough of a full-blown manic or depressive episode.

Lithium Corrects Circadian Rhythm Abnormalities in Bipolar Depression

April 2, 2021 · Posted in Current Treatments · Comment 
Young woman smiling

At a recent scientific meeting, researcher Monica Federoff described new findings about lithium’s effects in people with bipolar I disorder, especially regarding circadian rhythms. The 12-week study included 386 participants with bipolar I. Some participants responded well to lithium, but even those whose bipolar disorder did not remit saw improvements in total symptoms, depressive symptoms, and manic symptoms.

Only those who were classified as good responders to lithium treatment showed improvement in circadian symptoms. Their depression improved in the direction of more “morningness,” and the authors suggested that “stabilization of circadian symptoms of depression may be an essential feature of lithium’s therapeutic effects in [bipolar] I patients.”

Pilot Study of Pramipexole for Anhedonia Symptoms in Unipolar Depression

March 29, 2021 · Posted in Potential Treatments · Comment 
woman looking out window

At a recent scientific meeting, researcher Laura Hack described an open-label pilot study of pramipexole in participants with major depression including anhedonia, or inability to feel pleasure. Five participants with prominent anhedonia and major depression completed eight weeks of treatment with pramipexole, which activates dopamine D2 and D3 receptors. Four of the five who completed the study saw notable improvements in their anhedonia and quality of life.

The starting daily dose was 0.26 mg, which was increased every three days to a target dose of 2.0 mg per day. Two additional patients dropped out due to side effects (nausea, poor sleep, and headache).

Low activity in the ventral striatum, a part of the brain associated with decision-making and implicated in the brain’s reward system, correlated with the severity of the patients’ anhedonia. These results suggest that further studies are warranted.

Pramipexole has also shown positive effects in two small studies in bipolar depression. The drug is currently approved by the US Food and Drug Administration for the treatment of Parkinson’s disease and also works in restless legs syndrome.

A Novel Drug Shows Promise in the Treatment of Negative Symptoms of Schizophrenia

March 24, 2021 · Posted in Potential Treatments · Comment 
man sitting near railway tracks

At a recent scientific meeting, Kenneth Koblan, Chief Scientific Officer at Sunovion Pharmaceuticals, Inc. reported on a new drug in development, SEP-363856, and its effects on negative symptoms of schizophrenia.

In both a 4-week double-blind study of participants with acute schizophrenia and in an open (non-blind) 6-month extension study, SEP-363856 was effective on negative symptoms. In the placebo-controlled acute study, those randomized to 50mg or 75mg of the drug showed improvement of moderate effect size in the following symptoms: blunted affect, avolition, anhedonia, asociality, and alogia. In the extension study, which consisted of 26 weeks of treatment with flexible doses (25/50/75 mg/day) of SEP-365846, patients improved further on multiple scales measuring negative symptoms.

SEP-363856 is a novel trace amine receptor 1 (TAAR1) agonist with serotonin 5-HT1A activity. Koblan and colleagues concluded, “These results suggest that activation of the TAAR1 receptor by SEP-363856, in the absence of D2 receptor blockade, may represent a promising approach to the treatment of negative symptoms in schizophrenia.”

Pimavanserin Prevents Relapse in Patients with Dementia-Related Psychosis

February 22, 2021 · Posted in Potential Treatments · Comment 
elderly man holds his head

At a recent scientific meeting, Erin Foff of Acadia Pharmaceuticals Inc. described a study of pimavanserin (a selective serotonin inverse agonist/antagonist at 5-HT2A receptors) in dementia-related psychosis. Pimavanserin is currently approved in the United States for the treatment of hallucinations and delusions associated with Parkinson’s disease (PD). There is currently no Food and Drug Administration–approved treatment for dementia-related psychosis.

Enrolled patients had moderate-to-severe psychosis associated with Alzheimer’s disease, Parkinson’s, dementia with Lewy bodies, vascular dementia, or frontotemporal dementia. After a 12-week open label phase with flexible dosing and a target dosage of 34mg/day, 217 of the participants with a good response to pimavanserin were then randomized to continue pimavanserin or switch to placebo. The study was stopped early when a prespecified interim analysis revealed that pimavanserin was clearly superior to placebo. There was a more than 2.8-fold reduction in risk of relapse with pimavanserin compared to placebo in the double-blind period. Those on higher doses of 34mg/day showed a more than 3.4-fold reduced risk of relapse. Acadia will seek FDA approval for pimavanserin for the treatment of dementia-related psychosis.

Lumateperone Improves Bipolar Depression Symptoms

February 18, 2021 · Posted in Potential Treatments · Comment 
elderly woman

At a recent scientific meeting, Suresh Durgam of Intra-Cellular Therapies, Inc. reported on a study of lumateperone tosylate for the treatment of bipolar depression. Lumateperone tosylate is a mechanistically novel antipsychotic that has been approved by the US Food and Drug Administration for the treatment of schizophrenia.

In a double-blind, placebo-controlled study, the drug showed efficacy in bipolar I and II depression. In a 6-week study, 377 patients received either 42 mg/day of lumateperone or placebo, and 333 (87.4%) completed treatment. Lumateperone treatment significantly improved total scores on the Montgomery Asberg Depression Rating Scale (MADRS) compared with placebo. Item analysis revealed that 8 of 10 MADRS items improved significantly in comparison with placebo by day 29, and all items did by day 43. The largest effects were in reported sadness, apparent sadness, inner tension and reduced sleep. Durgam and colleagues concluded that lumateperone at a dose of 42mg improves a broad range of symptoms in bipolar I and bipolar II depression.

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