Mood stabilisers lithium

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... 

The most common is augmentation is with the mood stabiliser lithium carbonate. Indeed, lithium may be effective as monotherapy for depression but is not preferred because of its adverse effect profile and need for plasma concentration monitoring. Its prescription in combination with antidepressants that have failed to produce remission is more usual and evidence suggests that up to 50% of patients who have not responded to standard antidepressants can respond after lithium augmentation. Addition of lithium requires careful titration of the plasma concentration up to the therapeutic range, with periodic checks thereafter and monitoring for toxicity (see p. 389). 

A study in 14 treatment-resistant depressed patients aged between 61 and 82 found that 7 showed eomplete improvement and 3 showed partial improvement, 3 to 21 days after lithium was added to treatment with the tricyclic or related antidepressants. Lithium adverse effects occurred in 6 patients 4 of whom stopped lithium as a result. One of them was successfully restarted at a lower dose. Tremor was the most frequent adverse effect, and reversible neurotoxicity with a stroke-like syndrome was the most severe. The antidepressants used were amitriptyline, doxepin, maprotiline and trazodone. A meta-analysis of 9 studies on the acute treatment of unipolar or bipolar depression indicated that the combined use of a mood stabiliser (lithium in 6 studies) and a tricyclic antidepressant was associated with an increased risk of switches into (hypo)mania, when compared with a mood stabiliser alone. It was suggested that monotherapy with a mood stabiliser should be tried to see if it is effective, before adding an antidepressant. Tricyclics were considered to be second-line antidepressants, with SSRIs the preferred choice. ... 

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). 

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. 

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. 

The least biased evidence on whether lithium and other mood stabilisers have antisuicidal properties comes from randomised controlled trials and this is negative. A large amount of data from studies of drug treatment of acute mania and relapse prevention found no difference in rates of suicide or suicide attempts between patients randomised to take mood stabilisers, including lithium, and those randomised to placebo (Storosum et al. 2005). 

Lithium has been used to treat bipolar disorders based on its mood stabilising effects for several decades. Considerable effort has been put into understanding the mechanism by which lithium operates. The recent discovery that lithium inhibits GSK-3 at therapeutic concentrations has introduced the possibility that GSK-3 represents a key target of lithium s action in the brain. 

Some dmgs used as mood stabilisers (see Chapter 5) also have antidepressant properties (lithium in unipolar and probably bipolar depression, lamotrigine in bipolar depression) with a lack of evidence for others even though they are commonly used first line in bipolar depression (valproate, carbamazepine). 

The term mood stabiliser has been applied to lithium and antieonvulsant dmgs used to treat bipolar disorder. It is also starting to be applied to some atypieal antipsychotics. Its use has become more controversial with developments in anticonvulsant and atypical antipsychotic use in bipolar disorder. 

Lithium and sodium valproate are the most commonly prescribed mood stabilisers, used for ... 

Mood stabilisers should be withdrawn over one to three months (especially lithium)... 

Explain you ll still support her if she decides to go medication-free, but it s generally safer to withdraw mood stabilisers (especially lithium) slowly, to reduce the relapse risk... 

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