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CPD 46: BIPOLAR DISORDER IN ADULTS

TREATMENT Pharmacological The management of bipolar disorder can be split into three phases: 1. Treatment of a manic or hypomanic episode 2. Treatment of a depressive episode 3. Long-term management and prevention of symptoms returning Educational distance

Module 1 June 2012

Bipolar disorder

learning content for healthcare professionals in Ireland

Manic or hypomanic episodes

Chronic Pain – assessment and management in primary care

Episodes of mania usually require hospital admission to protect patients from behaviour that may place them, or others, at risk of harm. Any drug that might have contributed to the presentation, such as antidepressants, will need to be stopped to prevent prolonged symptoms. Antidepressants are usually stopped abruptly in mania but a gradual tapered withdrawal may be appropriate in those with less severe symptoms to avoid antidepressant discontinuation problems (e.g. influenza-like symptoms, dizziness and insomnia).

an antipsychotic with either lithium or valproate, or valproate with lithium. Depressive episodes

significant risk or adverse consequences, those who have had two or more episodes of mania or depression, or sufferers with significant functional impairment, risk of suicide or frequent episodes.

Most patients with bipolar disorder have far more depressive episodes than manic ones but, Specific drug monitoring considerations until recently, bipolar depression was poorly The treatment of choice for a first episode researched and most of the treatment options Lithium - has a narrow therapeutic range and of mania or hypomania includes an atypical were extrapolated from unipolar depression. so requires close monitoring of plasma levels antipsychotic, a valproate preparation or lithium Bipolar depression often occurs more rapidly, and other physical health parameters, such as if symptoms are less severe. The four atypical more frequently and with more marked renal and thyroid function. Blood levels should antipsychotics currently licensed for treating symptoms than unipolar depression and, for ideally be taken 12 hours after a dose (10–14 mania are aripiprazole, olanzapine, risperidone Sheehan et al reported in aiming 1996 that estimated many, it is a life-long illness rather than one that Introduction hours at most) for athe level betweencost of and quetiapine. These atypical antipsychotics occurs in discrete episodes. pain for 95 0.6–1mmol/L. patients to theLevels Irish Health when added above Services 0.75mmol/L offer are generally preferred because of their more Pain is one of the commonest reasons for patients to seek additional protection manic symptoms to the amount of Social Welfare against payments received and favourable short-term adverse effects. As such, antidepressants have a role in treating 1 surveydepression has shownbut that as many medical attention. A recentbipolar but come with a greater burden of adverse should be used with the lost earnings Valproate is available in as three theyear to primary effects.of each patient amounted to 1.9 million caution because of theinrisk of causing mania or 8.3forms visits in per care physicians Ireland UK: sodium valproate, valproic acid and pounds at the time of referral.6 The recent data from PRIME hypomania (“switching”). They should always due to symptoms of pain.2 A large scale survey carried Lithium toxicity generally occurs above semi-sodium valproate. were In Ireland, only be prescribed in conjunction with an antimanic survey show that the mean per chronic pain patientof 1.5mmol/L and iscost associated with symptoms sodium valproate, valproic licensed.countries outacid in 15are European andtoIsrael in 2006, screening agent reduce this risk. If an antidepressant is estimatednausea, at €5,665 per year across all grades of pain, diarrhoea, course tremor, drowsiness Sodium valproate and semi-sodium valproate is necessary, selective serotonin 46,394 respondents reported that the prevalence of chronicreuptake ataxia. Because lithium almost are metabolised to valproic acid, which is which was and extrapolated to €5.34 billionis or 2.86% of Irish inhibitors (SSRIs) are recommended because pain of moderate toof severe intensity in adult Europeans was exclusively excreted unchanged in urine, any responsible for the pharmacological activity 7 they have a lower risk of switching (3.7 per cent) GDP per year. an urgent need for cost 3 drugThis that demonstrates alters renal handling or electrolyte the drug. Although only 19%. semi-sodium valproate compared with the tricyclic antidepressants effective strategies to manage chronic pain effectively. balance can increase lithium levels and hence is licensed for acute mania, it is generally (11.2 per cent) and, most probably venlafaxine. cause toxicity. This includes angiotensinunclear if there is any effiMore cacy recent or tolerability survey data from another study, carried out converting enzyme inhibitors, thiazide diuretics In rapid cyclers and those with a mixed difference between the preparations. What is 2,019 people with chronic pain and 1,472 primaryare likely to increase Understanding chronicantipain disorder, antidepressants and non-steroidal inflammatory drugs. important is the dose ofin valproate. For rapid the switching rate andhave as such should be Dehydration and a low salt diet can also raise symptom control (i.e. within few days) aacross 15 European careaphysicians countries, Chronic is defined pain and that are outlasts normal healing avoided. In those for whom an antidepressant is pain lithium levelsas rapidly important points loading dose of 20mg/kg/day is occasionally demonstrated that chronic not painappropriate, affects 12-54% of adult quetiapine (at 300mg per day) for consideration. used but at the expense of increased adverse time (usually three to six months), and is most frequently Europeans, and its prevalence in Ireland is up to 13%. The depression, or lamotrigine (unlicensed in2bipolar reactions. associated with musculoskeletal disorders such as low of Erratic compliance or abrupt discontinuation but the usual dose is 50–200mg per day) are PRIME (Prevalence, Impact and Cost of Chronic Pain) study, lithium should be actively discouraged because Lithium is effective in acute mania but its onset back pain and arthritis. However, it can also be associated recommended. In contrast to treatment for on the other determined the prevalence chronic this may increase the risk of a manic relapse. of action is slower than that seen withhand, atypical unipolar depression,of antidepressant treatment with other disorders such as depression or metabolic 4 antipsychotics or valproate. to high this isas 35.5% pain Added to be as Ireland. The PRIME studyshort-term. in in bipolar depression is usually has recently been the as subject of a disorders orLithium neurologic conditions such multiple the need for pre-lithium physical health checks, bipolar management National Patient Safety Agency (NPSA) alert in was designed to investigateSome the prevalence of chronic guidelines pain which may be refused by patients who are recommend that the antidepressant should sclerosis. which, the importance of regular plasma levels, in Ireland; compare the psychological physical health acutely unwell and frequently uncooperative be tapered and off and then withdrawn after eight physical health monitoring and problematic and in a state of treatment decline. weeks of symptom However, Pain this (acuteinteractions profiles of those with and without chronic pain;remission. and explore or chronic) can categorised as nociceptive werebe highlighted. Lithium levels approach is variable and will ultimately depend pain-related disability. should be measured every three months, The short-term use of benzodiazepines, such 4 Responses to survey questions were or neuropathic. Nociceptive pain is caused by an active on the management approach implemented by however in practice they are frequently only as lorazepam or clonazepam, are from also useful obtained 1,204 people. the treating clinician. illness, injury and/or inflammatory process associated with checked following a dose adjustment or during in acute mania for their calming and sedative actual or potential tissue damage i.e. Nociceptive pain an episode of acute illness. effects. Long-term management

Despite the magnitude of the problem, chronic pain is

results fromValproate activity in-neural pathways to actual is a major humansecondary teratogen and If a patient presenting with mania or hypomania andThe goal of long-term treatment both under-recognised undertreated in primary care.2,5is to prevent so should be avoided in pregnancy. As the or potential tissue damage. Nociceptive pain is mediated is already on an appropriate antimanic new mood episodes and to increase the Indeed, up to 38% of patients reported beingbetween inadequately associated fetalinabnormalities occur in early medicine, clinicians should first check period of stability episodes. Targeting by pain receptors located skin, musculoskeletal system, pregnancy, ideally it should be avoided in managed in primary their pain symptoms. In knowing the compliance before considering optimising thecare for predominant symptoms2and 8 bone, and joints. Neuropathic pain, onpotential. the otherIfhand, any woman of child-bearing an treatment by increasing addition, the dose people or indeed course of the illness is essential for effective with chronic pain reported waiting up to pregnancy occursor while a woman is results fromunplanned direct injury to a peripheral central sensory switching the choice of treatment. If the maintenance. NICE recommends long-term 2.2 years between help and should diagnosis, and 1.9 for those response is inadequate then medicines are seekingtreatment taking valproate, she should be advised to seek be considered nerve; the affected nerves do not produce transduction at 2 often combined. Common combinations years before theirinclude pain waswho adequately managed. have suffered a manic episode involving immediate specialist advice. 8

nociceptors. Pain characteristics and associated conditions for both types of pain are shown in Table 1.

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