Acute antidepressive efficacy of lithium monotherapy, not citalopram, depends on recurrent course of depression.

Studies of the 1970s and 1980s showed lithium monotherapy to be an effective treatment of acute unipolar major depressive disorder (MDD) and hence as a potential alternative to monoaminergic antidepressants.The objective was to conduct the first comparison of a lithium monotherapy with a modern antidepressant in the acute treatment of MDD. Results were compared with citalopram's efficacy as shown in a different but methodologically identical study (including same researchers, same time, and same place).Thirty patients with an acute MDD (Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM IV] I) were treated with lithium monotherapy (study 1) or with citalopram monotherapy (study 2, N = 32) for 4 weeks.Response rates (decrease in Hamilton Depression Rating Scale score >50%) were 50% for lithium and 72% for citalopram (P = 0.12). Citalopram-treated subjects showed a greater decrease in Hamilton Depression Rating Scale scores (significant at 2 weeks). In the lithium study, only patients with a recurrent episode (DSM-IV: 296.3) responded (15/22), as opposed to none of 8 patients with a first/single episode (DSM-IV: 296.2) (P = 0.002). Patients with a single episode responded significantly more often to citalopram than to lithium (P = 0.007). Both drugs were well tolerated. Only one patient (citalopram) terminated the study prematurely owing to adverse effects.Our results do not support the use of lithium as an alternative to SSRI in the treatment of acute MDD. The finding of a better response to lithium in patients with a recurrent depression has not been reported before and warrants replication. The comparison is limited by the lack of a randomized double-blind design.

Impact of citalopram on the HPA system. A study of the combined DEX/CRH test in 30 unipolar depressed patients.

BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system is one of the best replicated pathophysiological findings in depression. However, studies on the influence of treatment on the HPA system have partly yielded inconsistent results. OBJECTIVE: To assess the effects of citalopram monotherapy on the HPA system of mainly drug naïve patients with major depression by means of the combined DEX/CRH test. METHODS: The DEX/CRH test was conducted twice in 30 patients (25 drug naïve for the index episode) with major depression (single episode or unipolar recurrent; SCID I- and II-confirmed): directly before the start of a citalopram monotherapy (day 0) and four weeks thereafter (day 28). RESULTS: Twenty-three patients responded (≥50% reduction in the HDRS(21)-score), and 17 of them also reached criteria of remission (HDRS ≤ 7). Baseline (dexamethasone-suppressed) and CRH-stimulated ACTH concentrations significantly decreased from day 0 to day 28. CRH-stimulated cortisol concentrations also fell, although not significantly, but baseline cortisol concentrations exhibited a significant increase from day 0 to day 28. CONCLUSIONS: The blunting of the ACTH response in the DEX/CRH test under citalopram is in line with what has been observed in most studies with antidepressants. However, the partial rise in cortisol concentrations indicates an increase in the sensitivity of the adrenal cortex to ACTH. State-dependent alterations in the volume and the ACTH responsiveness of the adrenal gland have repeatedly been reported in depressed subjects, which indicates the possibility that SSRIs such as citalopram might exhibit a direct or indirect effect on the adrenal cortex.

Lithium monotherapy increases ACTH and cortisol response in the DEX/CRH test in unipolar depressed subjects. A study with 30 treatment-naive patients.

BACKGROUND: Distorted activity of the hypothalamic-pituitary-adrenocortical (HPA) system is one of the most robustly documented biological abnormalities in major depression. Lithium is central to the treatment of affective disorders, but little is known about its effects on the HPA system of depressed subjects. OBJECTIVE: To assess the effects of lithium monotherapy on the HPA system of patients with major depression by means of the combined DEX/CRH test. METHOD: Thirty drug-naive outpatients with major depression (single episode or unipolar recurrent; SCID I- and II-confirmed) were treated with lithium monotherapy for four weeks. The DEX/CRH test was conducted directly before intake of the first lithium tablet and four weeks thereafter. Weekly ratings with the HDRS(21) were used to determine response (≥50% symptom reduction) and remission (HDRS ≤7). RESULTS: Lithium levels within the therapeutic range were achieved rapidly. Tolerability was good; no patient terminated the treatment prematurely. Response and remission rates were 50% and 33% respectively. Compared to the DEX/CRH test before the start of the treatment, a considerable and significant increase in all CRH-stimulated ACTH and cortisol parameters could be detected in the second DEX/CRH test. When analysed with particular regard to responders and non-responders, that significant increase was only present in the responders. CONCLUSIONS: We were able to demonstrate that lithium leads to a significant activation of the HPA system. This is possibly connected to stimulation of hypothalamic arginine vasoporessin (AVP), to direct intracellular effects of lithium on pituitary cells and to an induction of gene expression. TRIAL REGISTRATION: drks-nue.uniklinik-freiburg.de DRKS00003185.

Withdrawal phenomena and dependence syndrome after the consumption of "spice gold".

BACKGROUND: "Spice" and other herbal blends were marketed in Germany until January 2009 as substances purportedly exerting similar effects to cannabis, yet containing no cannabinoids. These products were recently forbidden in Germany under the provisions of the German Narcotics Law after they were found to contain undeclared, synthetic cannabinomimetic substances. The authors describe physical withdrawal phenomena and a dependence syndrome that developed after the consumption of "Spice." CASE PRESENTATION AND COURSE: A 20-year old patient reported that he had smoked "Spice Gold" daily for 8 months. He developed tolerance and rapidly increased the dose to 3 g per day. He felt a continuous desire for the drug and kept on using it despite the development of persistent cognitive impairment. His substance use led him to neglect his duties in his professional training position. Urinary drug screens were negative on admission to the hospital, as they were again on discharge. On hospital days 4-7, he developed inner unrest, drug craving, nocturnal nightmares, profuse sweating, nausea, tremor, and headache. His blood pressure was elevated for two days, with a maximal value of 180/90 mm Hg accompanied by a heart rate of 125/min. The patient stated that he had experienced a similar syndrome a few weeks earlier during a phase of abstinence owing to a short supply, and that it had quickly subsided after he had started consuming "Spice" once again. CONCLUSIONS: The authors interpret the symptoms and signs described above as a dependence syndrome corresponding to the ICD-10 and DSM-IV criteria for this entity. The physical withdrawal syndrome closely resembles that seen in cannabis dependence. The authors postulate that the syndrome in the patient described was due to an admixture of synthetic cannabinomimetics such as JWH-018 and CP 47497 in "Spice Gold," in combination with the patient's daily consumption in very large amounts.