As mood stabilisers

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. 

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. 

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 use of antidepressants has been discouraged because of their ability to switch patients into mania, hence they are not viewed as 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). 

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. 

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). 

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). 

THC (0.1 mg/kg) was reported to have anti-depressant properties in cancer patients (Regelson et al. 1976). There are anecdotal reports that cannabis may act as a mood stabiliser in bipolar affective disorder (Grinspoon and Bakalar 1998). 

A recent suggestion is that drugs can be classified as those that treat from Above (i.e. mania), called type A mood stabilisers, those that treat from Below (i.e. depression), called type B mood stabilisers, and those that are both A and B. Some advocate simply referring to drags antimanic or anti-depressive properties. 

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. ... 

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