lithium-chloride and Mental-Disorders

Lithium use in mental diseases has changed over the years but remains a cornerstone of treatment in bipolar disorders. In two companion papers, we have reviewed existing (and especially recent) data on lithium efficacy and updated basic knowledge regarding the practical fundamentals of lithium therapy. The present paper reviews safety data on lithium available to date. Gastrointestinal pain or discomfort, diarrhoea, tremor, polyuria, nocturnal urination, weight gain, oedema, flattening of affect and exacerbation of psoriasis are typical complaints of patients receiving long-term lithium therapy. Renal involvement results in a reduced urinary concentrating capacity, expressed as obligate polyuria, with secondary thirst. With long-term therapy, this may result in nephrogenic diabetes insipidus. In addition, glomerular filtration rate falls slightly in about 20% of patients. The view that only a few patients receiving long-term lithium are at increased risk of glomerular impairment and progressive renal insufficiency should be regarded with caution. The risk is increased in case of concomitant diseases or medications. Lithium treatment may inhibit thyroid hormone release and induce goitre. Consequently, the prevalence of both overt and subclinical hypothyroidism is increased, with circulating thyroid auto-antibodies frequently being found. Much less commonly, thyrotoxicosis may also develop in association with lithium therapy. Long-term lithium treatment may also be associated with persistent hyperparathyroidism and hypercalcaemia, as well as with hypermagnesaemia. Overweight of up to 4-10 kg is found in approximately 30% of lithium-treated patients. Most neurological manifestations are benign, for example, the fine postural and/or action tremor present in 4-20% of patients. This is increased by high caffeine consumption and concomitant use of other psychotropic agents. A number of rare, potentially serious neurological adverse effects have been reported, including extrapyramidal symptoms, 'pseudotumour cerebri' or occasionally cerebellar symptoms. Severe neurological sequelae are exceptional. Cognitive disturbances are often mentioned as a lithium-related adverse effect. The few controlled studies do show a statistically significant negative effect of lithium on memory, vigilance, reaction time and tracking. There are frequent reports of mild effects of lithium on cognition at therapeutic serum concentrations. A number of deaths associated with lithium trea

Topics: Age Factors; Antimanic Agents; Central Nervous System Diseases; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; Female; Humans; Kidney Diseases; Lactation; Lithium Chloride; Male; Mental Disorders; Metabolic Diseases; Pregnancy; Sex Factors; Thyroid Diseases

Serendipity is one of the many factors that may contribute to drug discovery. It has played a role in the discovery of prototype psychotropic drugs that led to modern pharmacological treatment in psychiatry. It has also played a role in the discovery of several drugs that have had an impact on the development of psychiatry. "Serendipity" in drug discovery implies the finding of one thing while looking for something else. This was the case in six of the twelve serendipitous discoveries reviewed in this paper, i.e., aniline purple, penicillin, lysergic acid diethylamide, meprobamate, chlorpromazine, and imipramine. In the case of three drugs, i.e., potassium bromide, chloral hydrate, and lithium, the discovery was serendipitous because an utterly false rationale led to correct empirical results; and in case of two others, i.e., iproniazid and sildenafil, because valuable indications were found for these drugs which were not initially those sought The discovery of one of the twelve drugs, chlordiazepoxide, was sheer luck.

Topics: Animals; Anti-Anxiety Agents; Antimanic Agents; Drug Industry; Hallucinogens; History, 19th Century; History, 20th Century; Humans; Lithium Chloride; Lysergic Acid Diethylamide; Mental Disorders; Penicillins; Pharmacology; Piperazines; Psychotropic Drugs; Purines; Sildenafil Citrate; Sulfones; Terminology as Topic; Vasodilator Agents

Previous research has suggested that both lithium and buspirone could lessen alcoholics' desire to drink as well as reduce the actual amounts of alcohol consumed. The purpose of this study was to compare lithium and buspirone monotherapy with placebo on outcomes of abstinence, alcohol quantity consumed, treatment retention and compliance, and medication side effects.. We conducted a randomized, double-blind, placebo-controlled, three-arm parallel group, clinical trial that compared lithium and buspirone with placebo in 156 alcohol-dependent men.. Study retention rates for the three treatment groups at 3 and 6 months, respectively, were 61% and 46% for lithium, 44% and 27% for buspirone, and 52% and 38% for placebo (p = NS, for 3 and 6 months). Overall abstinence rates were 28% and 19% at 3 and 6 months, respectively. However, mean daily quantities of alcohol consumed and percentage of drinking days decreased significantly (p < 0.0001) over time in all treatment groups. Differential improvement was seen only for the decrement in quantity consumed in the buspirone group, compared with the placebo group, but only at a trend level (p = 0.07). According to pill counts, compliance did not differ significantly among the treatment groups.. These results do not support the hypothesis that either lithium or buspirone, compared with placebo, produces differential reductions in alcohol consumption. The results suggest the need to enhance treatment retention to maximize outcomes.

Topics: Adult; Alcoholism; Anti-Anxiety Agents; Antimanic Agents; Buspirone; Double-Blind Method; Humans; Lithium Chloride; Male; Mental Disorders; Middle Aged; Regression Analysis; Temperance

To avoid poisoning and death when toxins are ingested, the body responds with a suite of physiological detoxification mechanisms accompanied by behaviours that in mammals often include vomiting, nausea, and lethargy. Few studies have characterised whether insects exhibit characteristic 'malaise-like' behaviours in response to intoxication. Here, we used the honeybee to investigate how intoxication produced by injection or ingestion with three toxins with different pharmacological modes of action quinine, amygdalin, and lithium chloride affected behaviour. We found that toxin-induced changes in behaviour were best characterised by more time spent grooming. Bees also had difficulty performing the righting reflex and exhibited specific toxin-induced behaviours such as abdomen dragging and curling up. The expression of these behaviours also depended on whether a toxin had been injected or ingested. When toxins were ingested, they were least 10 times less concentrated in the haemolymph than in the ingested food, suggesting that their absorption through the gut is strongly regulated. Our data show that bees exhibit changes in behaviour that are characteristic of 'malaise' and suggest that physiological signalling of toxicosis is accomplished by multiple post-ingestive pathways in animals.

Topics: Amygdalin; Animals; Bees; Dose-Response Relationship, Drug; Female; Flight, Animal; Grooming; Lithium Chloride; Locomotion; Mental Disorders; Motor Activity; Multivariate Analysis; Neurotoxins; Quinine; Sucrose

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Clozapine; Humans; Lithium Chloride; Male; Mental Disorders; Neutropenia

Previous study has indicated that chronic treatment with lithium protects brain against ischemic injury by reducing apoptotic death. To investigate whether lithium improves the behavioral disorder induced by transient global cerebral ischemia, we examined the effects of lithium treatment on the performance of rats in a set of behavioral tests, i.e. beam balance, elevated plus maze (EPM), open field and Morris water maze. Our results showed that lithium attenuated the worse general 'well-being' and the worse performance in beam balance, and hyperactivity in EPM and open field, including increased open arm entries, time spent in the open arms, squares crossed, rearing and grooming over 7 days after 15min ischemia, which were induced by four-vessel occlusion in Sprague-Dawley rats. Moreover, lithium improved the injured spatial learning and memory ability in Morris water maze at post-ischemic days 8 and 9. Histological analysis displayed that it decreased obviously cell death in hippocampal CA1 region. Our study further confirmed the protective role of lithium in the ischemia-reperfusion injury and suggested that lithium might be a helpful therapeutic approach to the treatment of stroke combining with other neuroprotective agents.

Topics: Animals; Antipsychotic Agents; Behavior, Animal; Cell Count; Disease Models, Animal; Exploratory Behavior; Hippocampus; Ischemic Attack, Transient; Lithium Chloride; Male; Maze Learning; Mental Disorders; Psychomotor Performance; Rats; Rats, Sprague-Dawley; Survival Rate; Time Factors

Topics: Adolescent; Antidepressive Agents; Antimanic Agents; Child; Conduct Disorder; Depressive Disorder; Ethics, Medical; Female; Humans; Lithium Chloride; Male; Mental Disorders; Mentally Ill Persons; Placebos; Randomized Controlled Trials as Topic; Research Design

Lymphocyte subset levels and function were examined in 12 patients on lithium therapy and in 11 healthy hospital personnel. Co-culture of allogeneic human bone marrow cells with monocyte-depleted lymphocyte preparations revealed that CFU-C formation was significantly reduced (mean 43% inhibition) in the presence of normal lymphocytes but not with the patients' lymphocytes (less than 5% inhibition). This did not reflect numerical changes in lymphocyte subsets, since these were similar for control and lithium subjects. T colony formation was significantly depressed in the patient group (P less than 0.05), whereas B colony numbers were similar in both groups (P greater than 0.1). The possible role of HLA-incompatibility affecting CFU-C growth was investigated in co-culture experiments, using lymphocytes from HLA-identical twins, one of whom was receiving lithium. In four separate co-culture experiments, the inhibitory effect was shown with lymphocytes from the non-lithium twin but was not demonstrated by the lithium subject. Addition of lithium in vitro to co-cultures of normal marrow and lymphocytes was found to negate the inhibitory phenomenon in a dose-related manner. It is postulated that granulocytosis induced by the administration of lithium may be a manifestation of changes in a lymphocytic control system.

Topics: Adult; Aged; B-Lymphocytes; Bone Marrow Cells; Cells, Cultured; Chlorides; Colony-Forming Units Assay; Diseases in Twins; Female; Humans; Lithium; Lithium Chloride; Lymphocytes; Male; Mental Disorders; Middle Aged; T-Lymphocytes; Twins, Monozygotic