Mood stabilizers - lithium

Fluoxetine L-dopa Mazindol Metronidazole Non-steroidal anti-inflammatory drugs (NSAIDs) 

Muscle relaxants (including those used during ECT pancuronium bromide, succinylcholine bromide, vancuronium bromide) 

Chlorpromazine (lithium delays its gastric emptying with a consequent longer exposure to gut wall catabolic enzymes) 

Alcohol Antipsychotic drugs (APDs) Benzodiazepines Carbamazepines Clozapine Diltiazem ECT 

Legend E 1 Drugs that can 1 increase the serum 1 levels/effects of r lithium E fc Dmgs whose serum ACEI I levels/effects can be 1 increased by 1 lithium Angiotensin-converting enzyme inhibitor Electroconvulsive therapy 

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If we dehne a mood stabilizer as a medication that is both an effective anti-manic and antidepressant, then lithium arguably remains to this day the prototypical mood stabilizer. Lithium not only reduces the symptoms of acute BPAD, it also prevents the recurrence of additional mood episodes. Despite the fact that lithium has revolutionized the treatment of BPAD and remains nearly 50 years after its introduction as the single best treatment for many patients with BPAD, there is still no consensus as to how it works. Lithium exerts effects on several neurotransmitter systems (e.g., serotonin, dopamine, norepinephrine, acetylcholine), on second messenger systems inside the nerve cell, and on nerve cell gene expression. Yet, precisely how these varied effects produce lithium s therapeutic benefit remains unclear. 

Lithium remains the treatment of choice for bipolar patients who experience classic euphoric episodes of mania. Current evidence suggests that those with mixed episodes or rapid cycling episodes respond preferably to anticonvulsants or atypical antipsychotic drugs. In addition to its use as a mood stabilizer, lithium is effective in converting unipolar antidepressant nonresponders to responders. Finally, lithium may also be an effective treatment for patients with clnster headaches. 

Mood Stabilizers. Lithium (Eskalith, Lithobid), valproic acid (Depakene), sodium valproate (Depakote), and carbamazepine (Tegretol) are most often used by psychiatrists to treat the bipolar disorders. These so-called mood stabilizers are also used to treat impulsivity and agitation in a variety of psychiatric disorders including dementia, certain personality disorders, and the disruptive behavior disorders of childhood. 

The mood stabilizer lithium was developed as the first treatment for bipolar disorder. It has definitely modified the long-term outcome of bipolar disorder because it not only treats acute episodes of mania, but it is the first psychotropic drug proven to have a prophylactic effect in preventing future episodes of illness. Lithium even treats depression in bipolar patients, although it is not so clear that it is a powerful antidepressant for unipolar depression. Nevertheless, it is used to augment antidepressants for treating resistant cases of unipolar depression. 

Immediately after remission of an episode of mania treated with perphenazine + a mood stabilizer (lithium, car-bamazepine, or valproate), patients were randomly assigned to 6 months of double-blind treatment in which, in addition to the mood stabilizer, they received either continued perphenazine (n = 19) or placebo (n = 18) (113). There were no between-group differences in various important demographic and clinical characteristics. Those given placebo were more likely than those who... 

Following remission of manic symptoms in 37 patients who had taken perphenazine and a mood stabilizer (lithium, carbamazepine, or valproate), treatment was randomly assigned double-blind to perphenazine or placebo for 6 months, while continuing the mood stabilizer (1). Those who took perphenazine had worse outcomes than those who took placebo, in that they were more likely to have a shorter time to a depressive relapse, were more likely to discontinue treatment, or were more likely to have depression or extrapyramidal symptoms. The authors tentatively concluded that perphenazine may not be beneficial in maintenance treatment for bipolar I patients. 

Combinations of amphefamines with mood stabilizers (lithium, anticonvulsants, atypical anfipsychotics) is generally something for experts only, when monitoring patients closely and when other options fail... 

Mood Stabilizers (Lithium and Anticonvulsants). Due to the lack of evidence demonstrating their benefit, lithium and anticonvulsants are reserved for BN patients with a comorbid bipolar affective disorder. Target serum concentrations and doses are similar to those used for patients with seizure or mood disorders. Lithium must be used cautiously, because purging and laxative abuse increases the risk of toxicity. The adverse effect of weight gain often makes mood stabilizers and anticonvulsants unacceptable to patients in the long term. 

Yasuda S et al (2009) The mood stabilizers lithium and valproate selectively activate the promoter IV of brain-derived neurotrophic factor in neurons. Mol Psychiatry 14(1) 51—59... 

All in all, compared with the well-established group of mood stabilizers (lithium, carbamazepine, and valproate), topiramate is currently considered the least potent/efficacious in ameliorating both manic and/or depressive symptoms (see Section 2.22). 

Blood levels clearly correlate with therapeutic response for a minority of the psychotropic drugs, including the antipsychotics haloperidol, clozapine, and olanzapine the tricyclic antidepressants and the mood stabilizer lithium. 

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

The first mood stabilizer was lithium (its antimanic action being discovered in 1948) more recently the anticonvulsant drugs carbamazepine and valproate have been found to be effective in acute mania. Unfortunately these mood stabilizers are only successful in controlling mania to a limited extent and few patients are well enough to leave hospital at the end of 3 weeks of treatment using these drugs as monotherapy. It is increasingly common for combination treatment to be advocated, in which an antipsychotic dmg is combined with lithium or an anticonvulsant. 

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... 

Optimize the dose of mood stabilizing medication(s) before adding on lithium, lamotrigine, or antidepressant (e.g., bupropion or an SSRI) if psychotic features are present, add on an antipsychotic ECT used for severe or treatment-resistant depressive episodes or for psychosis or catatonia... 

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. 

Increasing evidence shows an effect of lithium on suicidal behavior that is superior to other mood-stabilizing drugs.28 Lithium reduces the risk of deliberate self-harm or suicide by about 70%. 

It is common for lithium to be combined with other mood-stabilizing drugs or antipsychotic drugs, if necessary, in order to achieve more complete remission of symptoms. Studies indicate that monotherapy is often insufficient to reach this goal.17... 

Lithium and other mood-stabilizing drugs require baseline and routine laboratory monitoring to help determine medical appropriateness for initiation of therapy and monitoring of potential adverse effects. Guidelines for such monitoring are outlined in Table 36-6. 

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... 

Introduced in clinical practice in the 1960s, lithium was the first mood stabilizer to be used in China. This was followed by carbamazepine and sodium valproate. For many years, these were the only treatment options available as mood stabilizers. Although lamotrigine was approved for maintenance treatment of bipolar I disorder in 2003 by FDA (Food and Drug Administration) in the USA, this indication has not yet been approved by the Chinese authorities. At present, only one atypical antipsychotic drug, risperidone, has been approved for treating acute mania (February 2005 by SFDA [State Food and Drug Administration]) in China (see Table 6.1). 

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