Case report: Hyperactive delirium after a single dose of zolpidem administered additionally to psychopharmacotherapy including clozapine.

The non-benzodiazepine hypnotic zolpidem is frequently administered as a short term psychopharmacotherapy for insomnia. Although it is well-established in a broad clinical routine and often well-tolerated, severe delirium and complex sleep behavior were reported in rare cases. Hereby, it remains unclear whether zolpidem's potential for delirium might be enhanced when combined with further psychopharmacotherapeutics. The present case report portrays a young male Caucasian inpatient with schizoaffective disorder, who was admitted due to severe hyperactive delirium after a single dose of zolpidem 10 mg that was administered in addition to already established psychopharmacotherapy including clozapine 200 mg/day, aripiprazole 15 mg/day and cariprazine 4.5 mg/day. In detail, disorientation, agitation, confabulations, bizarre behavior, and anterograde amnesia occurred shortly after ingestion of zolpidem and gained in intensity within a couple of hours. Once zolpidem was discontinued, the abovementioned symptoms subsided completely and did not reoccur. Since a clear temporal association could be drawn between the intake of zolpidem and the onset of hyperactive delirium, the present clinical experience should serve as a cautionary note for combining potent sedative-hypnotics and substances with anticholinergic properties, even in young adults in a good general condition. Moreover, our case argues for the necessity of further research into the pathomechanism of the interaction potential of non-benzodiazepines as zolpidem, especially with substances exerting anticholinergic properties, which are known for their potential to precipitate delirium. Therefore, the metabolic pathways of the concurrently administered substances should be further taken into account.

Intravenous esketamine leads to an increase in impulsive and suicidal behaviour in a patient with recurrent major depression and borderline personality disorder.

Objectives: As clinical studies demonstrated that ketamine possesses rapid-acting antidepressant and antisuicidal effects, it is increasingly used in affective disorders. The neuroplastic properties of ketamine are well described in preclinical and imaging studies, and are highly related to its antidepressive mechanism of action.Methods: Here, we report on a female patient with recurrent major depression and borderline personality disorder (BPD) who was treated with intravenous (i.v.) esketamine as rapid-acting augmentation therapy to improve severe and acute depressive symptoms and suicidal behaviour.Results: Esketamine led to an initial improvement of these symptoms. However, during the course of treatment, loosened and disinhibited behaviour and severe suicidal ideation occurred during and immediately after esketamine application. Hence, i.v. esketamine was discontinued, and she further received treatment as usual, which demonstrated to be beneficial.Conclusions: With current knowledge at hand, one cannot exclude esketamine's effects on the equilibrium of neural plasticity in brain networks, potentially initiating undesirable symptoms as impulsive behaviour and emotional dysregulation. Therefore, until investigations focus on efficacy and side effects profile of esketamine in depressed patients with (comorbid) BPD, treatment with this fast-acting medication should be considered with caution in this patient group.

Combination of intravenous S-ketamine and oral tranylcypromine in treatment-resistant depression: A report of two cases.

Ketamine, a rapid-acting antidepressant and anti-suicidal agent, is thought to increase brain monoamine levels by enhancing monoamine release or inhibiting presynaptic monoamine-reuptake. Here we present two female inpatients suffering from treatment-resistant depression with recurrent severe suicidal crises receiving a combination of intravenous S-ketamine and oral tranylcypromine, which is a well-known irreversible monoamine oxidase (MAO) inhibitor. Since inhibition of monoamine-reuptake with concurrent blockade of MAO might trigger sympathomimetic crisis, this combination is considered hazardous. Nonetheless, cardiovascular parameters remained stable in both patients, while good anti-suicidal effects were observed. Hence, we put serious doubt on whether monoamine-reuptake inhibition is a relevant pharmacological effect of ketamine in humans.

Actigraphic measurements in opioid detoxification with methadone or buprenorphine.

The objective of the present naturalistic study was to assess the differential effects of opioid detoxification with methadone or buprenorphine on activity, circadian rhythm, and sleep. Forty-two consecutive inpatients with opiate addiction were switched to either methadone or buprenorphine and gradually tapered down over the course of 2 to 3 weeks. There were no significant differences in comedication (lofexidine, quetiapine, and valproic acid) between the methadone and buprenorphine groups. Patients in the methadone group showed 11% lower activity and were 24 minutes phase delayed as compared with buprenorphine-treated patients, whereas the latter had 2.5% lower sleep efficiency and 9% shorter actual sleep time. These significant group differences were most pronounced for the lowest doses (≤20% of maximum individual daily dose, ie, at the end of withdrawal representing late withdrawal effects). Furthermore, for the total sample, we found a significant decrease in the relative amplitude of the sleep-wake cycle and worsening of all actigraphic sleep parameters from the higher (100% to 20%) to the lowest doses (20% to 0%). The acrophase of the circadian rhythm displayed a phase advance (-88 minutes) from the highest (100% to 80%) to the lower doses (80% to 0%) in methadone-treated patients. Opioid tapering with methadone or buprenorphine leads to characteristic changes of the rest-activity cycle, but further study is required to validate these results.

Self-poisonings with tricyclic antidepressants and selective serotonin reuptake inhibitors in Tehran, Iran.

In a prospective hospital-based cohort study, we addressed the question of severity and outcome of antidepressant poisonings in patients who attended the Loghman-Hakim Hospital Poison Center, the only national center in Tehran dedicated for detoxification. The aim of the study was to find out if tricyclic antidepressant (TCA) intoxications require more therapeutic efforts than selective serotonin reuptake inhibitor (SSRI) intoxications. The study was applied over a 7-week period (28 March-20 May 2006). From 3578 intoxications, 334 patients with antidepressant or lithium self-poisoning were identified (9.3% of all poisoning cases; 233 females, 101 males; median age 24 years, min 13, max 70). Compared to SSRI single-substance intoxications (n=17), TCA single-substance intoxications (n=73) were associated with: (1) a significantly lower level of consciousness (P=0.005); (2) a significantly higher admission frequency (80.8 vs. 35.3%; P<0.001); and (3) a higher intubation frequency (13.7 vs. 0%; P=ns). SSRI multiple-substance intoxications were associated with a significantly lower level of consciousness than SSRI single-substance intoxications (P=0.042), while there was no significant difference between TCA multiple- and single-substance intoxications. This study suggests that an overdose with SSRIs results in a more favourable clinical outcome than an overdose with TCAs.

Effect of intravenous magnesium sulphate in reducing irritability and restlessness in pure and polysubstance opiate detoxification.

The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of intravenous magnesium sulphate (MgSO(4)) on the need for chlormethiazole in pure or polysubstance opiate detoxification. Forty-one inpatients suffering from pure and polysubstance opiate dependence were treated with morphine sulphate pentahydrate in a gradual detoxification program. Morphine reduction took about 11 days. Additionally, 5% MgSO(4) was administered intravenously to the intervention group (Mg group, n=22) over 24 h by perfusor (150-200 mg MgSO(4)/h; plasma level of 2.36+/-0.29 mmol/l), whereas NaCl 0.9% was intravenously administered in the placebo group (n=19). In case of withdrawal symptoms (irritability, restlessness, and insomnia), patients received chlormethiazole p.o. Our hypothesis that the need for chlormethiazole would be decreased by adjunctive administration of Mg was not confirmed in our study population (2180 mg/day in the Mg group vs. 2360 mg/day in the placebo group). There was neither a difference in the quantity of chlormethiazole required nor a difference in the severity of withdrawal symptoms measured with the Wang scale between the two comparison groups. We observed that calcium plasma levels decreased and phosphate plasma levels increased significantly during intravenous therapy with Mg. Despite promising pilot studies, the administration of Mg did not enable a dose reduction of tranquilizing medication (chlormethiazole) in pure and polysubstance opiate detoxification.