Hypomania lithium

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 are several controlled trials of young outpatients with bipolar and bipolar spectrum conditions. Geller et al. (1998) studied 25 adolescents in a 6-week, doubleblind, placebo-controlled study. Twelve received lithium, of whom 4 had BP-I (presumably acute mania), 4 had BP-II (presumably hypomania), and 4 had major depression with bipolar predictors. All had concurrent substance abuse. There were no significant differences in outcome between active and placebo groups, except in... 

Note. BP = bipolar disorder D/C = discontinue Dep = depression Li = lithium M = mania SA = schizoaffective RBD = recurrent brief depression UP = unipolar. Drug-induced hypomania. 

It is worthwhile noting that the combined treatment of T4 and lithium for patients with rapid-cycling bipolar disorder is reported to be more effective than lithium alone [Whybrow 1994], whereas T4 by itself is not effective and in high dosages may even cause hypomania or manic states. 

Consensus Development Panel 1985] confirmed that lithium salts were efficacious and should especially be considered for those considered unipolar but with a family history of bipolar disorder, because perhaps as many as 15% of patients with unipolar depression do subsequently experience hypomania or mania. Lithium may be the ideal maintenance agent for such uncertain patients for whom there is concern that administration of antidepressants may precipitate highs or increase the frequency of cycling and for those who dislike side effects of some antidepressant groups. 

Barak Y, Levine J, Behnaker RH Effects of inositol on lithium induced EEG abnormalities. Eur Neuropsychopharmacol 4 419-420, 1994 Barczak P, Edmunds E, Betts T Hypomania following complex partial seizures. Br J Psychiatry 152 137-139, 1988... 

By contrast, a number of studies have not found verapamil monotherapy to be effective for acute mania (Table 10-14). Several case reports in the literature have not supported verapamil s potential antimanic properties. For example. Barton and Gitlin ( 262) found that none of eight acutely manic or hypomanic patients treated openly improved on verapamil. By contrast, there are several case reports of hypomania (some monoamine oxidase inhibitor—induced) improving with verapamil. Dubovsky (255) notes that, in his experience with spontaneous mania, he has been unimpressed with verapamil in patients who had previously been unresponsive to lithium. 

Lithium carbonate and lithium citrate are the most commonly used compounds. Lithium has effects on cation transport, on individual neurotransmitters (including 5-HT) and on intracellular second messenger systems. Which of these is key to its therapeutic efficacy is not entirely clear but, as for the antidepressant drugs, the net effects seem to be to enhance serotonin function and to stabilise the noradrenergic system. Once lithium treatment is established it is very important that it is not suddenly stopped as this may result in rebound hypomania. 

Lithium not only treats acute episodes of mania and hypomania but was the first psychotropic agent shown to prevent recurrent episodes of illness. Lithium may also be effective in treating and preventing episodes of depression in patients with bipolar disorder. It is least effective for rapid cycling or mixed episodes. Overall, lithium is effective in only 40 to 50% of patients. Furthermore, many patients are unable to tolerate it because of numerous side effects, including gastrointestinal symptoms... 

Neurologic adverse effects of lithium include reduced reactivity, lack of spontaneity, intellectual insufficiency, memory problems, difficulty in concentration, dysphoria. Some of these effects may be related to the therapeutic action of lithium in reducing hypomania. However, hypothyroidism, weakness and fatigue due to hypercalcemia, and breakthrough depression must be considered in the presence of these symptoms. 

Bipolar disorder is characterized by episodes of mania or hypomania, which include hyperactivity, decreased need for sleep, and a euphoric or irritable mood. Additionally, persons with bipolar disorder may have episodes of depression similar to those seen in major depressive disorder. The lifetime prevalence of severe bipolar disorder is about 1% and 3-5% if milder cases are included, afflicting men and women equally. Both bipolar disorder and major depressive disorder tend to be episodic, and in the periods of time between episodes, persons may experience few or no symptoms. The etiology of bipolar disorder is predominately genetic, with a 70% concordance in monozygotic twins. The neurobiology of bipolar disorder is less well understood, and few animal models have been developed. Treatment of bipolar disorder usually involves mood stabilizer medications, including lithium, and the anticonvulsants valproate and carbamazepine. At times, antidepressant and antipsychotic medications are also used. 

Indications and use. Lithium carbonate is effective treatment in > 75% of episodes of acute mania or hypomania. Because its therapeutic action takes 2-3 weeks to develop, lithium is generally used in combination with a benzodiazepine such as lorazepam or diazepam (or with an antipsychotic agent where there are also psychotic features). 

Professional opinions about lithium vary by discipline and by individual clinician. Some therapists find it easier to support the use of a "natural" substance, whereas others have been influenced by reports of side effects and toxicity. While the acutely manic patient is most often hospitalized, patients with hypomania or cyclothymia may be initiated on medications as outpatients, making the therapist an important part of the stabilization process. In this role, the therapist can assist the patient in assessing response and identifying side effects. 

Lithium is used for the prophylactic control of mania and hypomania and bipolar depression. It also has a use in unipolar depression that is unresponsive to other antidepressants. 

In an open study of 13 major depressive patients who did not respond to a 4-week eourse of venlafaxine 300 mg daily, lithium was added and continued for 4 weeks. After 12 days of combined treatment, 2 patients experienced symptoms of hypomania, marked nausea and trembling (considered to be a moderate form of the serotonin syndrome), and had to stop lithium treatment. Their lithium-plasma levels were within the thera-peuhc range (0.83 and 0.77 mmol/L on day 7). Lithium was well tolerated by most of the other patients, with trembling being the most frequent adverse effect (4 out of 11). ... 

---