Mood stabilisers

Treatment of Manic—Depressive Illness. Siace the 1960s, lithium carbonate [10377-37-4] and other lithium salts have represented the standard treatment of mild-to-moderate manic-depressive disorders (175). It is effective ia about 60—80% of all acute manic episodes within one to three weeks of adrninistration. Lithium ions can reduce the frequency of manic or depressive episodes ia bipolar patients providing a mood-stabilising effect. Patients ate maintained on low, stabilising doses of lithium salts indefinitely as a prophylaxis. However, the therapeutic iadex is low, thus requiring monitoring of semm concentration. Adverse effects iaclude tremor, diarrhea, problems with eyes (adaptation to darkness), hypothyroidism, and cardiac problems (bradycardia—tachycardia syndrome). 

Monophasic Preparations Monoxide Mood Disorders Mood Elevators Mood-stabilising Drugs Morbus Alzheimer Morphogens Morpholines Motilin... 

Turning to the pharmacotherapy for mania, for decades lithium was the only effective drug treatment. More recently, a number of antiepileptic drugs including carba maze pine, lamotrigine and valproate have been shown to also act as mood stabilisers and are becoming established for the treatment and prophylaxis of both unipolar mania and bipolar manic depressive disorders. 

The first two antidepressants, iproniazid and imipramine, were developed in the same decade. They were shown to reverse the behavioural and neurochemical effects of reserpine in laboratory rodents, by inhibiting the inactivation of these monoamine transmitters (Leonard, 1985). Iproniazid inhibits MAO (monoamine oxidase), an enzyme located in the presynaptic neuronal terminal which breaks down NA, 5-HT and dopamine into physiologically inactive metabolites. Imipramine inhibits the reuptake of NA and 5-HT from the synaptic cleft by their transporters. Therefore, both of these drugs increase the availability of NA and 5-HT for binding to postsynaptic receptors and, therefore, result in enhanced synaptic transmission. Conversely, lithium, the oldest but still most frequently used mood stabiliser (see below), decreases synaptic NA (and possibly 5-HT) activity, by stimulating their reuptake and reducing the availability of precursor chemicals required in the biosynthesis of second messengers. 

Mood stabilisers are used to regulate the cyclical change in mood characteristic of bipolar disorder, since they can attenuate both manic and depressive phases. Their main use is as a prophylactic for manic depression and unipolar mania. However, they can also be administered concomitantly with antidepressants for refractory (non-responsive) unipolar depression. 

Outline the clinical uses and side effects of mood-stabilising drugs. 

Chen G, Jiang Y et al. The mood stabilising agent valproate inhibits the activity of glycogen synthase kinase 3. J Neurochem 1999 72 1327-1330. 

There is no empirical evidence available for clinical use in children and adolescents. Yet, Hypericum seems to be used for the treatment of mild to moderate depression in the young (Walter et ah, 2000). St. John s wort should be avoided in young patients with severe depression and bipolar disorder (given the lack of adult data about effectiveness and risk of manic induction, respectively) and in those who have significant suicide risk. Treatments of proven efficacy (e.g., SSRIs, mood stabilisers) should be preferred in these cases. However, St. John s wort may be considered in cases of unipolar depression where conventional treatments have failed and prior to the use of combinations of drugs that have an increased risk of side effects and whose efficacy has not been demonstrated. 

Antidepressants for minor and major depressive disorders and mood stabilisers (anfimanic drugs) for mania. 

These drugs are most commonly classified according to their principal pharmacological effect rather than by specific chemical structure (Table 10.4). The exception to this is the tricyclic antidepressants which share a common chemical structure and also common pharmacological effects. The other important type of drug used in the treatment of mood disorders is the mood stabilisers (lithium compounds and some anticonvulsants) which are discussed in the next section of this chapter. Tricyclic antidepressants... 

Herman E. Lamotrigine a depression mood stabiliser. Eur Neuropsychopharmacol. 2004 14(suppl 2) S89—S93. 

What had once been a relatively rare disorder, for which there was considered to be only one very specific treatment is now regarded as a widespread problem with an array of new drug treatments. In addition, the concept of the mood stabiliser allows drugs for manic depression to be used in many other situations in which there appears to be some instability of mood. Since almost by definition acute psychiatric disorders involve extreme emotional responses, almost any psychiatric patient can qualify for treatment with a mood stabiliser. My clinical experience suggests the use of these drugs among psychiatric patients has expanded considerably. 

Although it was only a model, the idea of kindling superficially appeared to provide a disease-specific justification for the use of anticonvulsants in manic depression. It also opened up the possibility of defining a sort of drug that would reduce emotional reactivity, in the same way that anticonvulsants are believed to reduce the brain s nervous excitability. In this sense kindling gave birth to the notion of a mood stabiliser. However as David Healy has pointed out, it was not until Abbott laboratories started to research and market sodium valproate for manic depression that the idea of a mood stabiliser really took root (Healy 2006). 

In the next section, I will review the major research on lithium and other drugs currently used as mood stabilisers. Despite the greater sophistication of recent research, its interpretation is as much evidence of wishful thinking as the presentation of Cade s early experiments with lithium. 

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