62 - Withdrawal effects from lithium and other moo

Withdrawal effects from lithium and other mood stabilisers

Bipolar disorder CHAPTER 2 Stopping lithium and mood stabilisers Rationale for stopping Patients may ask to stop lithium and other mood stabilisers because of the range of adverse effects experienced. In one cohort 54% of patients discontinued lithium, mostly because of tolerability problems, including diarrhoea (13%), tremor (11%), polyuria/ polydipsia/diabetes insipidus (9%), creatinine increase (9%) and weight gain (7%).1 Alternatively, although lithium and mood stabilisers are useful in controlling acute symptoms and in preventing relapse, a clinician may judge that the balance of risks and benefits has shifted over time (e.g. adverse physical effects accumulate, alternative coping strategies developed) such that dose reduction or stopping may be considered. Other patients may be prescribed mood stabilisers for conditions such as personality disorders, for which there is a lack of evidence. Stopping should be done in a manner that minimises the risk of both withdrawal effects and relapse (the two key risks). Withdrawal effects from lithium and other mood stabilisers Discontinuation of lithium can cause withdrawal effects, including both physical and psychological symptoms (Table 2.13). These withdrawal effects include mood episodes (depression, but more commonly mania) and are sometimes called ‘rebound’ effects.2,3 The risk of relapse in the period following abrupt cessation greatly exceeds the rate of relapse in the untreated disorder.2 For example, a review of studies of lithium discontinuation in people with bipolar disorder found that the untreated disorder had a mean cycle length (the average time between episodes) of 11.6 months, whereas the time to a new episode following lithium discontinuation was 1.7 months.2 This represents a sevenfold increase in the rate of relapse and suggests that manic and depressive symptoms that occur following lithium withdrawal are largely because of lithium withdrawal effects rather than because of the untreated disorder. Nonetheless, it is to be expected that the withdrawal of an effective mood stabiliser leads to mood destabilisation simply because of the removal of an effective treatment for the condition. Relapse may sometimes indicate the need for continued treatment. Distinguishing between withdrawal-­related rebound and true relapse of the underlying condition is made easier by extending the withdrawal period (so as to help rule out withdrawal effects). Withdrawal effects are thought to be due to the development of dopaminergic hypersensitivity6 and changes in neuronal membranes, cell transport function or other neurotransmitter systems during lithium treatment.7 Other mood stabilisers have also been associated with a withdrawal syndrome.8 Table 2.13  Withdrawal effects of lithium.3–5 Physical effects Psychological effects Tremor Polyuria Muscular weakness Polydipsia Dryness of mouth Anxiety Nervousness Irritability Alertness Sleep disturbances Elated mood/mania Depressed mood