Serotonergic medications, herbal supplements, and perioperative serotonin syndrome.

PURPOSE: Perioperative use of serotonergic agents increases the risk of serotonin syndrome. We describe the occurrence of serotonin syndrome after fentanyl use in two patients taking multiple serotonergic agents. CLINICAL FEATURES: Two patients who had been taking multiple serotonergic medications or herbal supplements (one patient taking fluoxetine, turmeric supplement, and acyclovir; the other taking fluoxetine and trazodone) developed serotonin syndrome perioperatively when undergoing outpatient procedures. Both experienced acute loss of consciousness and generalized myoclonus after receiving fentanyl. In one patient, the serotonin syndrome promptly resolved after naloxone administration. In the other patient, the onset of serotonin syndrome was delayed and manifested after discharge, most likely attributed to the intraoperative use of midazolam for sedation. CONCLUSION: Even small doses of fentanyl administered to patients taking multiple serotonergic medications and herbal supplements may trigger serotonin syndrome. Prompt reversal of serotonin toxicity in one patient by naloxone illustrates the likely opioid-mediated pathogenesis of serotonin syndrome in this case. It also highlights that taking serotonergic agents concomitantly can produce the compounding effect that causes serotonin syndrome. The delayed presentation of serotonin syndrome in the patient who received a large dose of midazolam suggests that outpatients taking multiple serotonergic drugs who receive benzodiazepines may require longer postprocedural monitoring.

Síndrome serotoninérgico por interacción entre linezolid y 5-hidroxitriptófano / Serotoninergic syndrome due to interaction between linezolid and 5-hydroxytryptophan

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Chronic treatment with a tryptophan-rich protein hydrolysate improves emotional processing, mental energy levels and reaction time in middle-aged women.

Common pharmacological treatments of mood disorders aim to modulate serotonergic neurotransmission and enhance serotonin levels in the brain. Brain serotonin levels are dependent on the availability of its food-derived precursor essential amino acid tryptophan (Trp). We tested the hypothesis that delivery of Trp via food may serve as an alternative treatment, and examined the effects of a Trp-rich, bioavailable dietary supplement from egg protein hydrolysate on cognitive and emotional functions, mood state, and sleep quality. In a randomised, placebo-controlled, parallel trial, fifty-nine mentally and physically healthy women aged 45-65 years received placebo (n 30) or the supplement (n 29) (both as 0.5 g twice per d) for 19 d. Emotional processing was significantly changed by supplementation, exhibiting a shift in bias away from negative stimuli. The results for the Affective Go/No-Go Task exhibited a slowing of responses to negative words, suggesting reduced attention to negative emotional stimuli. The results for the Facial Emotional Expression Rating Task also supported a shift away from attention to negative emotions and a bias towards happiness. An increase in arousal-like symptoms, labelled 'high energy', shorter reaction times and a slight benefit to sustained attention were observed in the treated subjects. Finally, when the supplement was taken 60-90 min before bedtime, a feeling of happiness before going to bed was consistently reported. In summary, daily consumption of a low-dose supplement containing bioavailable Trp may have beneficial effects on emotional and cognitive functions.

p-Hydroxyamphetamine causes prepulse inhibition disruption in mice: contribution of serotonin neurotransmission.

p-Hydroxyamphetamine (p-OHA) has been shown to have a number of pharmacological actions, including causing abnormal behaviors such as increased locomotor activity and head-twitch response in rodents. We have recently reported that intracerebroventricular (i.c.v.) administration of p-OHA dose-dependently induces prepulse inhibition (PPI) disruption in mice, which is attenuated by pretreatment with haloperidol, clozapine or several dopaminergic agents. Haloperidol and clozapine have affinities for serotonergic (especially 5-HT(2A)) receptors. To investigate the involvement of the central serotonergic systems in p-OHA-induced PPI disruption, herein we tested several serotonergic agents to determine their effects on p-OHA-induced PPI disruption. p-OHA-induced PPI disruption was attenuated by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT, a neurotoxin which targets serotonin-containing neurons) and p-chlorophenylalanine (PCPA, a serotonin synthesis inhibitor). p-OHA-induced PPI disruption was also attenuated by pretreatment with ketanserin (a 5-HT(2A/2C) receptor antagonist) and MDL100,907 (a selective 5-HT(2A) receptor antagonist). These data suggest that p-OHA-induced PPI disruption may involve increased serotonin release into the synaptic cleft, which then interacts with the post-synaptic 5-HT(2A) receptor.

The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study.

Case reports indicate that psychiatrists administered ±3,4-methylenedioxymethamphetamine (MDMA) as a catalyst to psychotherapy before recreational use of MDMA as 'Ecstasy' resulted in its criminalization in 1985. Over two decades later, this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct. Twenty patients with chronic posttraumatic stress disorder, refractory to both psychotherapy and psychopharmacology, were randomly assigned to psychotherapy with concomitant active drug (n = 12) or inactive placebo (n = 8) administered during two 8-h experimental psychotherapy sessions. Both groups received preparatory and follow-up non-drug psychotherapy. The primary outcome measure was the Clinician-Administered PTSD Scale, administered at baseline, 4 days after each experimental session, and 2 months after the second session. Neurocognitive testing, blood pressure, and temperature monitoring were performed. After 2-month follow-up, placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA. Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline. The rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group. There were no drug-related serious adverse events, adverse neurocognitive effects or clinically significant blood pressure increases. MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments.

Neurotoxic effects of ecstasy on the thalamus.

BACKGROUND: Neurotoxic effects of ecstasy have been reported, although it remains unclear whether effects can be attributed to ecstasy, other recreational drugs or a combination of these. AIMS: To assess specific/independent neurotoxic effects of heavy ecstasy use and contributions of amphetamine, cocaine and cannabis as part of The Netherlands XTC Toxicity (NeXT) study. METHOD: Effects of ecstasy and other substances were assessed with (1)H-magnetic resonance spectroscopy, diffusion tensor imaging, perfusion weighted imaging and [(123)I]2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane ([(123)I]beta-CIT) single photon emission computed tomography (serotonin transporters) in a sample (n=71) with broad variation in drug use, using multiple regression analyses. RESULTS: Ecstasy showed specific effects in the thalamus with decreased [(123)I]beta-CIT binding, suggesting serotonergic axonal damage; decreased fractional anisotropy, suggesting axonal loss; and increased cerebral blood volume probably caused by serotonin depletion. Ecstasy had no effect on brain metabolites and apparent diffusion coefficients. CONCLUSIONS: Converging evidence was found for a specific toxic effect of ecstasy on serotonergic axons in the thalamus.

Serotonin syndrome: a reported case.

We describe a patient treated with SSRI and Ldopa, who developed agitation, rigidity, hyperreflexia, restlessness, autonomic instability, fever and finally death. CSF examination, MRI of the brain, laboratory investigations, except for serum CK, glycemia and WBC, were normal. His condition was thought to result from an central serotonin activity. The serotonin syndrome occurs following the use of serotomimetic agents (serotonin reuptake inhibitors, tricyclic and tetracyclic antidepressants, tryptophan alone or in combination with monoamine oxidase inhibitors).