Pharmacology lithium

Pharmacology Lithium alters sodium transport in nerve and muscle cells, and effects a shift toward intraneuronal catecholamine metabolism. The specific mechanism in mania is unknown, but it affects neurotransmitters associated with affective disorders. Its antimanic effects may be the result of increases in norepinephrine reuptake and increased serotonin receptor sensitivity. Pharmacokinetics ... 

Pharmacologically, lithium as a drug does not lose its efficacy, and does not induce addiction or dependence. Consequently, lithium retains its full effect even if it has been administered for long periods (even years). Moreover, both the effects and side effects of lithium are completely reversible indeed, a mechanical switch-on and -off function of lithium s biochemical mechanism has been discussed, though the details of this remain unknown (Schafer 1998,... 

In noncancer-related pharmacology, GSK3 is inhibited by lithium at therapeutic concentrations, implying that the long-established effectiveness of lithium in the treatment of psychiatric mood disorders (and more recently as a neuroprotective agent) may be linked to GSK3 inhibition. Antipsychotics such as haloperidol... 

Fawcett J, Kravitz HM, McGuire M, et al Pharmacological treatments for alcoholism revisiting lithium andconsidering Buspirone. Alcohol Clin Exp Res 24 666-674,2000... 

Mechanism of Action Lithium s pharmacologic mechanism of action is not well understood and probably involves multiple effects. Possibilities include altered ion transport, increased intraneuronal catecholamine metabolism, neuroprotection or increased brain-derived neurotrophic factor, inhibition of second messenger systems, and reprogramming of gene expression.29... 

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. 

Pharmacotherapy is very important for treating Bipolar Disorder, and the use of mood stabilizers, such as lithium, is considered the standard of care. However, after you stabilize a person s mood, you may be left with a person who has not learned a great many life skills over the years precisely because of her or his disorder. Fortunately, cognitive behavioral therapy, including skills training, has been used effectively with bipolar clients after they have been stabilized pharmacologically. Obviously the person must be emotionally stable in order to learn new skills. 

Lithium has numerous pharmacologic effects. It is able to cross through sodium channels, competing with monovalent and divalent cations in cell membranes (AHFS, 2000). Animal studies have shown that lithium at a serum level of 0.66 + — 0.08 mEq/L can increase the amphetamine-induced release of serotonin (5-hydroxytryptamine [5-HT]) and the concentrations of a serotonin metabolite (e.g., 5-hydroxyindoleacetic acid [5-HIAA]) in the perifornical hypothalamus (PFH) of rats before and after chronic lithium chloride administration (Baptista et ah, 1990), a mechanism possibly involved in lithium s antidepressant effect. The precise neurobiological mechanisms through which lithium reduces acute mania and protects against recurrence of illness remain uncertain (Lenox and Hahn,... 

Diagnostic boundaries in juvenile-onset BD need to be defined, since children with hypomania or manic-like symptoms may be increasingly treated with mood stabilizers. In parallel, this would require more complex algorithms because very few controlled trials have been reported (Walkup, 1995). In contrast to the studies of adults reported in the literature, the pharmacological treatment of childhood bipolarity with anticonvulsants remains an understudied area. Carbamazepine appears to be less efficacious than valproate in adult rapid cycling, yet no studies have identified predictors of treatment response to CBZ or any other mood stabilizer (besides lithium) in a pediatric population. 

There is strong evidence that bipolar disorder is associated with SUD in adolescents (Wilens et ah, 1999) and that pharmacological interventions are an effective treatment for youth with SUD and bipolar disorder. Two studies, including one randomized controlled study, have reported that mood stabilizers, specifically lithium and valproic acid (Depakote), significantly reduced substance use in bipolar youth (Donovan and Nunes, 1996 Geller et ah, 1998). In addition, these agents are considered effective agents for the treatment... 

According to the Expert Consensus Panel for Mental Retardation Rush and Frances, (2000), the mainstays of the pharmacological treatment of acute mania or bipolar disorder in adults are anticonvulsant medications (divalproex, valproic acid, or carbamazepine) or lithium. Both divalproex or valproic acid and lithium were preferred treatments for classic, euphoric manic episodes. Divalproex or valproic acid was preferred over lithium and carbamazepine for mixed or dysphoric manic episodes and rapid-cycling mania. For depressive episodes associated with bipolar disorder, the addition of an antidepressant (SSRI, bupropion, or venlafaxine) was recommended. According to the Expert Consensus Panel, the presence of MR does not affect the choice of medication for these psychiatric disorders in adults. 

The treatment of the major depressive disorders such as unipolar and bipolar depressions was initially considered to be uniform, ffowever, with psychopharmacological advances, it has been demonstrated that the patients with bipolar depression may be partially responsive, at least prophylactically responsive, to lithium therapy, whereas the patients with unipolar depression are not as responsive (Abou-Saleh 1992). In addition, the treatment of depression may contribute through serendipity to the confirmation of a subgroup of patients with a bipolar disorder referred to as bipolar II. These patients, following treatment with antidepressants, will switch over to a hypomanic or fully manic phase resulting from pharmacological mechanisms. Thus, another subgroup of the bipolar disorder may be identified in the future. 

Lithium remains our most effective treatment for reducing the frequency and severity of recurrent affective episodes, but, despite extensive research, the underlying biological basis for the therapeutic efficacy of this drug remains unknown. Lithium is a monovalent cation with complex physiological and pharmacological effects within the brain. By virtue of the ionic properties it... 

---