Bipolar disorders Lithium

The molten carbonate fuel ceU uses eutectic blends of Hthium and potassium carbonates as the electrolyte. A special grade of Hthium carbonate is used in treatment of affective mental (mood) disorders, including clinical depression and bipolar disorders. Lithium has also been evaluated in treatment of schizophrenia, schizoaffective disorders, alcoholism, and periodic aggressive behavior (56). 

Lithium, divalproex sodium (valproate), aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are currently approved by the FDA for treatment of acute mania in bipolar disorder. Lithium, olanzapine, and lamotrigine are approved for maintenance treatment of bipolar disorder. Quetiapine is the only antipsychotic that is FDA approved for bipolar depression. 

In eight patients with bipolar disorder, lithium for 3 1 weeks increased neutrophil count by 88% and also caused a significant increase in CD34+ cells (although three patients had no increase in either) (343). 

There is increasing evidence that abnormalities in phospholipid signal transduction are important in bipolar disorder. To date, most of this evidence has come from investigations of the mechanisms of action of the established drugs for bipolar disorder— lithium and valproate. This evidence suggests that there are abnormalities in the lipid-related protein kinase signal transduction systems and also in the PLA2 and PLC systems (Manji et al., 1999 Manji Lenox, 1999 Ikonomov Manji, 1999 Stoll Severus, 1996). 

Lithium ion is commonly ingested at dosages of 0.5 g/d of lithium carbonate for treatment of bipolar disorders. However, ingestion of higher concentrations (5 g/d of LiCl) can be fatal. As of this writing, lithium ion has not been related to industrial disease. However, lithium hydroxide, either dHectly or formed by hydrolysis of other salts, can cause caustic bums, and skin contact with lithium haHdes can result in skin dehydration. Organolithium compounds are often pyrophoric and requHe special handling (53). 

Other Drugs. Agents not considered to be CNS stimulants yet employed for the treatment of certain types of depression includes lithium carbonate for the treatment of bipolar disorder. In most patients, lithium is the sole agent used to control manic behavior and is very effective (see... 

Although lithium is not a true antipsychotic drug, it is considered with the antipsychotics because of its use in regulating the severe fluctuations of the manic phase of bipolar disorder (a psychiatric disorder characterized by severe mood swings of extreme hyperactivity to depression). During the manic phase, the person experiences altered thought processes, which can lead to bizarre delusions. The drug diminishes the frequency and intensity of hyperactive (manic) episodes. 

Ms. Brawn comes to the mental health clinic for a followup visit. She is taking lithium to control a bipolar disorder. Ms. Brown tells you that she is concerned because her hands are always shaking and sometimes I walk like I have been drinking alcohol. Explain how you would explore this problem with Ms. Brown. 

The mood stabilizers were so called because they prevent recurrences of mood swings in people with bipolar disorder. The evidence for this is best with lithium, but is based on smdies carried out more than 20 years ago. However, recent naturalistic surveys tend to find that lithium is far less useful in general clinical practice than in research settings. Many patients discontinue lithium... 

In the case of carbamazepine the evidence suggests that its prophylactic efficacy is less than that of lithium (Greil and Kleindienst, 1999). For valproate there is no placebo-controlled evidence as yet to support its efficacy in the prophylaxis of bipolar disorder. The only large-scale study designed to elucidate this action was a failed trial in which neither lithium nor valproate was more effective than placebo in maintenance treatment over 2 years (Bowden et al, 2000). 

The total costs are likely to reflect the efficacy of treatment. In one industry-sponsored study (Keck et al, 1996b) treatment with lithium or valproate was compared in relation to classical, mixed and rapid-cycling disorder. Treatment with lithium was associated with lower costs than treatment with valproate for classical bipolar disorder, but treatment with valproate was associated with lower costs than treatment with lithium for mixed and rapid-cycling disorders. This is in keeping with the evidence that valproate is more effective than lithium for certain patients with rapid-cycling disorder and probably also for certain patients with mixed affective states. However, these associations are a guide to predicting response to treatment but are not very specific. 

Maj M, Pirozzi R, Magliano L, et al (1998). Longterm outcome of lithium prophylaxis in bipolar disorder 5-year prospective study of 402 patients a lithium clinic. Am J Psychiatry 155,30-5. 

The evidence base for clinical decisions based on cost-effectiveness for the affective disorders is less clear than for schizophrenia. In bipolar disorder the primary effectiveness of the mainstay treatments, lithium and anticonvulsant pharmacotherapy, is undergoing considerable revision (Bowden et al, 2000). Until this is clarified, cost-effectiveness studies are probably premature. Nevertheless the cost burden in bipolar disorder is qualitatively similar to that in schizophrenia, with in-patient costs being the primary burden and associated social costs in treated patients. The drug costs are even less than those for schizophrenia. In Chapter 5 John Cookson suggests there is little economic evidence to drive prescribing decisions. The in-patient burden does not seem to have altered with the introduction of lithium. The only drug-related study (Keck et al, 1996) showed an obvious difference in treatment costs only when lithium was compared with sodium valproate. Since these are both cheap drugs this is unlikely to influence clinical decisions. The main question is what impact... 

Depression and mania are both affective disorders but their symptoms and treatments are quite distinct. Mania is expressed as heightened mood, exaggerated sense of self-worth, irritability, aggression, delusions and hallucinations. In stark contrast, the most obvious disturbance in depression is melancholia that often co-exists with behavioural and somatic changes (Table 20.1). Some individuals experience dramatic mood swings between depression and mania. This is known as "bipolar disorder which, like mania itself, is treated with lithium salts or neuroleptics. 

Pharmacotherapy is the cornerstone of acute and maintenance treatment of bipolar disorder. Mood-stabilizing drugs are the usual first-choice treatments and include lithium, divalproex, carbamazepine, and lamotrigine. Atypical antipsychotics other than clozapine are also approved for treatment of acute mania. Lithium, lamotrigine, olanzapine, and aripiprazole are approved for maintenance therapy. Drugs used with less research support and without Food and Drug Administration (FDA) approval include topiramate and oxcarbazepine. Benzodiazepines are used adjunctively for mania. 

TABLE 36-5. Pharmacokinetics and Therapeutic Serum Concentrations of Lithium and Anticonvulsants Used in the Treatment of Bipolar Disorder... 

Divalproex sodium is comprised of sodium valproate and valproic acid. The delayed-release and extended-release formulations are converted in the small intestine into valproic add, which is the systemically absorbed form. It was developed as an antiepileptic drug, but also has efficacy for mood stabilization and migraine headaches. It is FDA-approved for the treatment of the manic phase of bipolar disorder. It is generally equal in efficacy to lithium and some other drugs for bipolar mania. It has particular utility in bipolar disorder patients with rapid cycling, mixed mood features, and substance abuse comorbidity. Although not FDA-approved for relapse prevention, studies support this use, and it is widely prescribed for maintenance therapy. Divalproex can be used as monotherapy or in combination with lithium or an antipsychotic drug.31... 

Lamotrigine is effective for the maintenance treatment of bipolar disorder. It is more effective for depression relapse prevention than for mania relapse. Its primary limitation as an acute treatment is the time required for titration to an effective dosage. In addition to maintenance monotherapy, it is sometimes used in combination with lithium or divalproex, although combination with divalproex increases the risk of rash, and lamotrigine dosage adjustment is required.37... 

Treatment of depressive episodes in bipolar disorder patients presents a particular challenge because of the risk of a pharmacologic mood switch to mania, although there is not complete agreement about such risk. Treatment guidelines suggest lithium or lamotrigine as first-line therapy.17,41 Olanzapine has also demonstrated efficacy in treatment of bipolar depression, and quetiapine is under review for approval of treatment of bipolar depression.42 When these fail, efficacy data support use of antidepressants. 

Geddes JR, Burgess S, Hawton K, et al. Long-term lithium therapy for bipolar disorder systematic review and meta-analysis of randomized controlled trials. Am J Psychiatry 2004 161 217-222. 

Turecki, G., Grof, R, Grof, E. etal. (2001). Mapping susceptibility genes for bipolar disorder a pharmacogenetic approach based on excellent response to lithium. Mol. Psychiatry, 6, 570-8. 

Lithium The first drug to be used in the treatment of unipolar mania and bipolar disorder. 

Chen G, Manji HK. Lithium regulates PKC-mediated intracellular cross-talk and gene expression in the CNS in vivo. Bipolar Disorders 2000 2 217-236. 

A 36-year-old male with a bipolar disorder is treated with lithium. Among the following adverse effects, which is associated with lithium treatment ... 

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