Dr. Mohammad SI Mullick

Dr. Mohammad SI Mullick General Psychiatrist and Child & Adolescent Psychiatrist,working as Professor in this field.

02/05/2025

Valbenazine Significantly Improves Tardive Dyskinesia in Older Adults Over Long-Term

Adults ages 65 and older with tardive dyskinesia (TD) given valbenazine for up to 48 weeks experienced substantial and sustained improvements in symptoms while maintaining psychiatric stability, according to a post-hoc analysis of two clinical trials.
The researchers wrote that valbenazine may be well suited for older patients with TD because it requires no titration to reach an effective, tolerable dose and is available as a sprinkle formulation that can be mixed with soft foods.They undertook the study to address the “relative paucity of information on valbenazine efficacy and safety in relation to increasing age” among individuals 65 and older.

Sajatovic and colleagues pooled data from 304 individuals (55 of whom were 65 or older) who had participated in one of two 48-week studies of valbenazine—one an open-label study and the other a blinded-dosing study comparing 40 mg or 80 mg dosing. Participants were assessed with two clinician-rated assessments, the Abnormal Involuntary Movement Scale (AIMS) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD), at baseline and at various points over 48 weeks.

Overall, 40% of older participants experienced a meaningful response to valbenazine (≥50% improvement in AIMS) at eight weeks, which rose to 65% at 24 weeks and 82% at 48 weeks; the improvements in older adults were comparable to those seen in younger participants. Similar strong and comparable improvements were seen with CGI-TD scores; in fact, at week 48, older adults were significantly more likely to have a CGI-TD score ≤2 than younger participants (93% versus 77% respectively).

There was no statistical difference in the prevalence of adverse events between younger and older participants, though a significantly higher percentage of older participants discontinued medication due to an adverse event compared with the younger subgroup (26% versus 13%, respectively). The most common adverse events were urinary tract infection, drowsiness, and headache.

The researchers wrote that this article reports on data indicating that once-daily valbenazine is effective and well-tolerated in the ≥65-year age group. Given the projected rates of population aging in the U.S. and globally, along with the increased risk of TD with older age and historic under representation of adults aged ≥65 years in clinical trials, these results address an important gap in TD research.

For more information, see the article:
Goldberg JF. Tardive Dyskinesia: Assessing and Treating a Debilitating Side Effect of Prolonged Antipsychotic Exposure. Psychiatric News 2025;56(3):https://doi.org/10.1176/appi.pn.2021.3.10

18/01/2025

Su***de Risk Among Patients With Depression Highest First Three Days After Discharge

Patients with depression who have been discharged from psychiatric hospitals have the highest risk of dying by su***de in the first three days after discharge, with some risk factors increasing that risk further, according to a recent published article in JAMA Psychiatry.

Aaltonen and colleagues reported that of all people dying by su***de, more than half had depression, and approximately 40% had been recently hospitalized. Therefore, people hospitalized for depression are at significant risk of su***de following their discharge. “Such a population with a distinct high-risk period in contact with psychiatric care forms a prioritizable target for selective su***de prevention,” they wrote.

The researchers used data from Finnish registers such as the Care Register for Health Care and Statistics Finland, which included information on hospital admissions, discharges, diagnoses, and causes of death. They identified all psychiatric hospitalizations for depression among participants aged 18 years and older from 1996 to 2017; patients with comorbid major psychotic disorder or bipolar disorder were excluded. Each patient was followed for up to two years after discharge. For those with multiple hospitalizations, each discharge marked the beginning of a new follow-up period.
A total of 193,197 hospitalizations occurred during the study period among 91,161 participants (56.2% female; mean age 44 years). A total of 1,219 men and 757 women died by su***de during the study period. Additional findings included the following:

•During the first three days after discharge, the su***de incidence rate was 6,062 per 100,000 person-years. The authors noted that this rate exceeded the rate within the general population in Finland by 330-fold.

•The su***de rate remained high throughout the first week after discharge (3,884 per 100,000 person-years on days four to seven), but then fell steadily, dropping to 478 per 100,000 person-years after one year.

•Individuals who were admitted to the hospital due to a su***de attempt by firearm or hanging had the highest risk of death by su***de in the first three days after discharge. Other factors associated with immediate su***de risk included severe or psychotic depression, severe illness with impaired function, a history of attempted su***de, male s*x, and age 40 and above.

•Some factors showed temporal trends. Having a higher household disposable income was associated with immediate su***de risk after discharge, but later it was associated with a lower risk compared with those with lower income. Individuals hospitalized with comorbid alcohol use disorder had a lower immediate su***de risk than those without, but then a higher risk over time.

“Although we found a decreasing trend over time, the high-risk post-discharge period still requires intensified attention,” the authors wrote. “Continuity of care and access to enhanced psychiatric outpatient care within days of discharge should be imperative.”

See the Article:
Aaltonen K, Sund R, Hakulinen C, Pirkola S, Isometsä E. Variations in Su***de Risk and Risk Factors After Hospitalization for Depression in Finland, 1996-2017. JAMA Psychiatry. 2024;81(5):506–515. doi:10.1001/jamapsychiatry.2023.5512.

10/01/2025

Mirtazapine and Vitamin B6 May Be Best Options for Antipsychotic-Induced Akathisia

Akathisia—a feeling of restlessness is often accompanied by movements like rocking or pacing—is a common side effect of antipsychotic medications. A meta-analysis report suggests that biperiden, mirtazapine, and vitamin B6 are the three most effective treatment options for antipsychotic-induced akathisia.

Gerolymos and colleagues compiled data from 15 randomized clinical trials testing potential pharmacotherapies for akathisia in people taking antipsychotics. The combined data included 492 patients, 324 of whom received an active drug and 168 received placebo. Ten medications were evaluated: biperiden, clonazepam, cyproheptadine, mianserin, mirtazapine, propranolol, trazodone, valproate, vitamin B6, and zolmitriptan.

The researchers noted that clinicians should be prudent about interpreting their results due to the small sample size, but offered the following findings:
• Six medications were found to be effective. They were the following, in decreasing order of strength: mirtazapine, biperiden, vitamin B6, mianserin, trazodone, and propranolol.
• Cyproheptadine may also be potentially effective, but there was not enough evidence to make a firm conclusion.
• Clonazepam, valproate, and zolmitriptan did not show effectiveness and are not recommended.

The authors wrote that Mirtazapine consistently ranked first in both the main analysis and all subgroup analyses. However, mirtazapine may be poorly tolerated due to its sedative effects and the potential for weight gain. Rather, they suggested that vitamin B6 may be the best option in terms of risk-benefit ratio, as it is very well tolerated. However, for patients with akathisia who also have depressive symptoms and insomnia, mirtazapine may be preferred.
The researchers also cautioned that “trazodone should be avoided in men who have specific hematologic or neurologic diseases (such as sickle cell anemia, multiple myeloma, leukemia, hypercoagulable states, or autonomic nervous system disorders) or in men with anatomical deformations of the pen*s.”

See the Article
Gerolymos C, Barazer R, Yon DK, Loundou A, Boyer L, Fond G. Drug Efficacy in the Treatment of Antipsychotic-Induced Akathisia: A Systematic Review and Network Meta-Analysis. JAMA Netw Open. 2024;7(3): e241527. doi:10.1001/jamanetworkopen.2024.1527.

07/01/2025

New Schizophrenia Drug Shows Marked Effect on Cognitive Deficits

Individuals with schizophrenia and cognitive deficits who were treated with the combination of xanomeline and trospium chloride showed clinically significant improvements in cognition compared with those receiving placebo, according to a recent published article. The results, pooled from two Phase 3 clinical trials, replicate cognitive benefits seen in smaller studies.
Xanomeline/trospium chloride was approved for use by the U.S. Food and Drug Administration (with the brand name Cobenfy) in September 2024 for the treatment of schizophrenia in adults. Cognitive deficits are a stubborn feature in many cases of schizophrenia that significantly affect long-term trajectory and daily functioning.

Lead researchers said “Collectively, the xanomeline/trospium clinical studies reflect the first time a monotherapy for the treatment of schizophrenia has shown a replicable cognitive benefit,”.

Across the two trials, 357 patients with acute schizophrenia were randomly assigned to receive oral xanomeline/trospium or placebo twice daily for five weeks. Most participants assigned to xanomeline/trospium were taking the maximum dosage of 125 mg/30 mg twice daily at week 5, with the remainder taking an intermediate dosage of 100 mg/20 mg. Participants completed a computerized assessment of four key cognitive domains (executive function, visual memory, sustained attention, and verbal recall and recognition) at baseline, week 3, and week 5. Overall, 137 participants had significant cognitive deficits at baseline. Among patients with cognitive impairment, those receiving xanomeline/trospium showed a significantly larger improvement in their cognitive scores from baseline to week 5 than the placebo group, with a calculated effect size of 0.54 (indicating a moderate level of improvement). The largest difference in performance between the xanomeline/trospium and placebo groups observed at week 5 was for verbal recall and recognition.The effect remained significant after accounting for changes in positive and negative symptoms—suggesting that the effect on cognition is independent of improvement in psychotic symptoms. As with previous studies, there was no evidence of cognitive benefit for xanomeline/trospium when analyzing the full sample of 357 participants.

Cobenfy is the first drug approved for schizophrenia that does not act on dopamine (D2) receptors in the brain; rather it targets muscarinic acetylcholine receptors in areas of the brain more central to the cognitive and behavioral symptoms of schizophrenia.

See that article:
Horan WP, Sauder C, Ramsay IS, Yohn SE, Keefe RSE, Davis VJ, Paul SM, Brannan SK .The Impact of Xanomeline and Trospium Chloride on Cognitive Impairment in Acute Schizophrenia: Replication in Pooled Data From Two Phase 3 Trials. Am J Psychiatry 2024. https://doi.org/10.1176/appi.ajp.20240076.

18/10/2023

Don’t Shut Down Conversations When Youth Present With ‘Trending’ Disorders, Psychiatrist Says

Youth increasingly rely on social media to diagnose themselves with a variety of psychiatric illnesses—a trend that has been met with more than a few raised eyebrows.

In a short Article, Rettew described how he works with youth with so-called “trending presentations” and cautions against the dangers of oversimplifying such cases.

• Ask patients direct questions about whether they have a specific diagnosis in mind, as well as the research that led them to this conclusion: “[I]t is common for my new patients to get a little sheepish when disclosing the source of their investigations, as most commonly the ideas come from social media platforms such as YouTube or TikTok rather than the medical textbooks that used to make medical students wonder about being stricken with lots of exotic ailments,” he described.

• Reject the tendency to dismiss or deny the patient’s narrative “because it does not fit our current scientific or political perspective”: “Science has shown us repeatedly that virtually everything when it comes to mental functioning—from common personality traits to psychopathology to gender typical behavior—comes from a complicated mash-up of mutually interacting genetic and environmental factors. These environmental contributors include things such as peers and media influences, and their presence in the mix should not immediately disqualify someone’s history as undeserving.”

• The more complicated a clinical situation appears, the more important it is to stick to the basics: Establish good rapport with the patient, be thorough, validate while maintaining some skepticism, and give yourself time to conceptualize, he said. “[I]n so doing, we may find that those supposed trending presentations are an accurate description of symptoms that have been long experienced and suppressed by the individual until they are living in an environment supportive enough for their expression. … Or maybe we find out that, indeed, someone really has been heavily influenced by what they have heard from a peer or seen on a social media video as part of developmentally appropriate needs to feel connected socially and developmentally appropriate introspection at this age about their identity,” he wrote.

The author concluded, “Rigid and oversimplistic thinking often fails us and our patients by closing conversations before they ever truly open. The pathways through which our patients find their way to our office are incredibly rich and diverse. We lump them into convenient boxes at our peril, virtually begging our patients to reveal to us the deficiencies of our mental shortcuts.”

See the article:
Rettew DC. Internet Inspired Self Diagnosis: A New Phenomenon Calling for An Old Approach. J Am Acad Child Adolesc Psychiatry 2023. http//doi.org./10.1016/j.jaac:2023.08.017.

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