A Question for Physicians
Do you know how to treat a patient with a persistent horrendous side effect to a single dose of the SSRI Lexapro 20mg?
A patient wrote me, asking if I know any physicians who have seen this syndrome and know how to treat it.
After a single dose: “Sleep is ruined, Can’t nap or wake up sick feeling, Constant feeling like I am in agony, Can’t focus / concentrate, Can’t regulate body temperature, loss of appetite and libido, Memory issues, Extreme fatigue, Unintentional a weight loss, Muscles usually twitching somewhere, and Abnormal breathing”.
If you have seen this type of reaction and/or know how to treat it, please send your email to Scott Mclean at sdmclean@shaw.ca and a cc to me (the Editor of this newsletter) at Robert.postmd@gmail.com. The patient has given his informed consent for this email to be posted on www.bipolarnews.org.
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C – May become important in the future
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We’re back!
After a pandemic-related hiatus, we’re back, and we hope to bring you articles regularly. For print subscribers, we hope to send out a single large issue in the coming months.
Paternal heroin self-administration in rats increases drug-seeking behavior in male offspring via miR-19b downregulation in the nucleus accumbens
Wenjing Gao et al reported in Neuropsychopharmacology (2025) that “paternal heroin self-administration in rats results in increased heroin-seeking behavior in F1 male offspring. This effect was replicated by zygotic microinjection of sperm RNAs from heroin self-administration-experienced rats, but not from yoked infusion pairs, highlighting the role of sperm non-coding RNAs changes induced by paternal drug-seeking behavior (and not by just passive receipt of heroin.) Analysis of non-coding RNA changes in the NAc [nucleus accumbens] and sperm of the F0 generation revealed a significant correlation in miRNA expression profiles, particularly the downregulation of miR-19b in both tissues, which was linked to the observed phenotype. The heightened heroin-seeking behavior in the male F1 generation could be reversed by supplementing synthetic miR-19b in F0 sperm RNA or introducing miR-19b into the NAc of F1 offspring. These findings suggest that sperm miRNAs like miR-19b mirror changes in brain miRNAs, participate in epigenetic transmission of acquired traits from F0 to F1, as well as in regulating heroin SA behavior of offspring.”
Editor’s Note: These data suggest that dad rats self administering heroin transmit a vulnerability to self administering heroin to their offspring. It does not occur if the dad rats merely get heroin passively. It is likely that these data could be extrapolated to humans. If so, there is a question of whether taking opiates for pain (administered by a nurse as opposed to self administrated) would transmit vulnerability to the offspring. In any event, it may be that a heroin addict who self administers the drug not only puts himself at risk but also his male offspring. This makes clear that methods of producing primary protection in offspring for opiate addiction deserve exploration
Dextromethorphan potentiates the anti-depressant effects of SSRIs
Maji et al reported in Psychiatry Research (2024) that dextromethorphan 30mg compared to placebo potentiated the antidepressant effects of SSRIs on all measures and had few side effects. It is FDA-approved to potentiate bupropion.
Now it looks like a more general property.
New Medication for PTSD Approved
The double-blind, phase 3 trial included 416 adults aged 18-65 years with a DSM-5 diagnosis of PTSD and symptoms for at least 6 months prior to screening.
Patients underwent a 1-week placebo-run in period followed by randomization to daily oral brexpiprazole 2-3 mg plus sertraline 150 mg or daily sertraline 150 mg plus placebo for 11 weeks.
Psilocybin Bests SSRI for Major Depression in First Long-Term Comparison
“MILAN — Psilocybin leads to a better overall outcome in the treatment of moderate to severe major depressive disorder (MDD) than the selective serotonin reuptake inhibitor (SSRI) escitalopram, results of the first long-term comparison of the two treatments suggest.
“This is the first work to compare the long-term effects of these two drugs in the context of overall well-being, not just freedom from depression,” study investigator Tommaso Barba, PhD, candidate Imperial College London, London, England, said in a press release. “Psilocybin outperformed escitalopram in several measures of well-being, meaning in life, work, and social functioning.”
Findings from the 6-month follow-up study of a phase 2 double-blind, randomized, controlled trial were presented on September 22 at the 37th European College of Neuropsychopharmacology (ECNP) Congress and published simultaneously in The Lancet eClinicalMedicine….The initial single-center study included 59 adults with MDD (mean age, 41 years) who were randomized to receive either psilocybin or escitalopram over a 6-week period. The psilocybin arm (n = 30) received two 25-mg oral doses of psilocybin therapy (PT), and the escitalopram arm (n = 29) received 10-20 mg of daily escitalopram plus two (placebo-like) 1-mg doses of psilocybin (ET). Both groups received psychological support….The researchers conclude that while a short course of SSRIs combined with intensive therapeutic support (around 20 hours) “might be enough to induce sustained antidepressant effects,” patients treated with psilocybin showed greater improvements in general functioning, connectedness, and meaning in life.
Although not reassessed in the follow-up, the initial study showed that adverse events, particularly sexual functioning, favored psilocybin, said Barba.”
Family History of Alcohol Dependence Predicts Antidepressant Response to an NMDA Antagonist
LE Phelps reported in Biol. Psy (2009) that subjects with a family history of alcohol dependence showed significantly greater improvement in MADRS scores compared with subjects who had no family history of alcohol dependence.
They concluded that a family history of alcohol dependence appears to predict a rapid initial antidepressant response to the NMDA receptor antagonist ketamine.
Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia
Kaul, et al noted in Jama Psi (2024) that “In this phase 3, double-blind, randomized, placebo-controlled trial in 256 people with schizophrenia, xanomeline-trospium was associated with a statistically significant and clinically meaningful reduction in Positive and Negative Syndrome Scale total score compared with placebo. Xanomeline-trospium was generally well tolerated; the most common adverse events were primarily gastrointestinal effects, which were mild or moderate in intensity and generally transient in nature.
EMERGENT-3 confirms previously reported clinical trials (EMERGENT-1 and EMERGENT-2) demonstrating that xanomeline-trospium is efficacious and well tolerated in people with schizophrenia experiencing acute psychosis. Xanomeline is a dual M1/M4 preferring muscarinic receptor agonist with no direct D2 dopamine receptor blocking activity. KarXT combines xanomeline with the peripheral muscarinic receptor antagonist trospium chloride with the goal of reducing adverse events due to xanomeline-related peripheral muscarinic receptor activation.”
Bipolar Disorder Patients Respond to Ketamine, Esketamine Treatment
(Reposted from the Yale School of Medicine blog)
A small sample of patients with bipolar disorder displayed noteworthy improvement in their depressive symptoms after being treated with the rapid-acting antidepressant intravenous ketamine and the nasal spray esketamine, according to a new Yale led-study.
The study, published October 2 in the Journal of Clinical Psychiatry, also found that patients were not at higher risk of suffering a manic episode during the acute phase of treatment.
Review: Reconsideration of bipolar disorder as a developmental disorder
Reconsideration of bipolar disorder as a developmental disorder: Importance of the time of onset
Pierre Alexis Geoffroy et al, J Physiology Paris, 2013
Eight admixture studies have demonstrated three homogeneous subgroups of patients with bipolar disorder, identi?ed by their age at onset (early, intermediate and late age at onset), with two cutoff points, at 21 and 34 years.
The early onset group had more: Suicide attempts, rapid cycling, drug and alcohol abuse, psychotic symptoms, panic disorder, OCD, and a positive family history for affective disorder. Early onset illness should be recognized and treated earlier.
Trace lithium levels in drinking water reduce the risk of dementia: a systematic review
International Journal of Bipolar Disorders volume 12, Article number: 32 (2024)
The sample size varied in the studies from 37,597 to 35,000,000. Lithium levels ranged from 0.002 to 0.027 (mg/L).
“We systematically reviewed five available studies, which reported associations between trace-Li in water and incidence [of] or mortality from dementia. Association between trace-Li levels and a lower risk or mortality from dementia were observed at concentrations of Li in drinking water as low as 0.002 mg/L and 0.056 mg/L. Meanwhile, levels below 0.002 mg/L did not elicit this effect. Although three of the five studies found dementia protective properties of Li in both sexes, a single study including lower Li levels (0.002 mg/l) found such association only in women.
Conclusion
The reviewed evidence shows that trace-Li levels in the water are sufficient to lower the incidence or mortality from dementia. Considering the lack of options for the prevention or treatment of dementia, we should not ignore these findings. Future trials of Li should focus on long term use of low or even micro doses of Li in the prevention or treatment of dementia.
