Organic disorders
1 Delirium Based on Delirium by Laura Gage and David K. Conn in Effective Treatments in Psychiatry, Cambridge University Press, 2008 Introduction Delirium needs treatment for both its causes and manifestations, as, if ignored, it is associated with excessive periods of hospitalization or early mortality. The common causes include infection, drug intoxication, renal or hepatic insufficiency, vascular disease affecting the brain, and (often forgotten) electrolyte disturbance. The main interventions are environmental and pharmacological and the symptoms on which they are focused are agitation, overactivity, restlessness, and other behavioural disturbance, and psychotic symptoms such as hallucinations, delusions, and paranoid reconstruction of the world. As might be expected, randomized controlled trials are very difficult to carry out in this population as the manifestations of delirium are acute and cannot be ignored, and most of the evidence of efficacy of interventions is based on less convincing models. Non-pharmacological interventions Delirium is very common in hospitalized patients, particularly after surgery and other interventions, and providing a consistent environment with the right level of stimulation has long been thought to avoid or reduce manifestations of delirium. Only one randomized trial has been carried out of 31 patients following 3
4 Organic disorders open heart surgery in an intensive care unit (Budd & Brown, 1974). Patients randomized to a specific reorientation procedure, focusing on time, place, person, and physical status, given by intensive care nurses, showed fewer symptoms of delirium, had significantly fewer postoperative complications, and were discharged from hospital an average of 4 days earlier compared with a control group of patients who did not receive this intervention but who had standard care. Other nonrandomized studies have supported these findings (Chatham, 1978; Williams et al., 1985; Milisen et al., 2001). A review by Cole et al. (1996) concluded that systematic interventions to stabilize the environment and offer support were more effective with older surgical patients compared with patients on medical units. A recent Cochrane Review of multidisciplinary team interventions in patients with chronic cognitive impairment concluded that although nine controlled trials were identified for possible inclusion in the review, only one (Budd & Brown, 1974) met the inclusion criteria. Despite the presumptive evidence from other studies they concluded that delirium is currently managed empirically and that there was no evidence in the literature to support changes to current practice (Britton & Russell, 2004). Despite the relative absence of good data supporting controlled environmental interventions the American Psychiatric Association still recommend them because of wide clinical experience and, perhaps more importantly, their lack of adverse effects (American Psychiatric Association, 1999). This has increased in importance as the technology of intensive care has improved and environments become less homely. Patients with delirium can become overstimulated by the excessive noise in such units. Similarly, if stimulation is too low delirium can also become more likely. Pharmacological interventions Typical antipsychotic drugs Only one randomized controlled trial has compared typical antipsychotics in delirium. Breitbart et al. (1996) compared the effectiveness of chlorpromazine, haloperidol, and lorazepam in hospitalized patients with AIDS. All included met diagnostic criteria for delirium and scored 13 or more on the delirium rating scale (DRS). Two hundred and forty-four patients were included and 30 of these subsequently developed delirium and were randomized to one of the three study medications. The efficacy of intervention was similar for haloperidol and
Delirium 5 chlorpromazine and improvement was noted within the first 24 hours. Those patients allocated to lorazepam developed major side effects but the mean daily dosage of the drug (4.6 mg) was much higher than the usual dosage. As there was no placebo control arm, haloperidol or chlorpromazine may not have performed better than no intervention. All other studies in the published literature are small and have weak methodology so no conclusions can be drawn. A combination of benzodiazepines and haloperidol was compared in a naturalistic study by Menza et al. (1988). It was noted that those who received the haloperidol and benzodiazepines had fewer extrapyramidal symptoms than those who received haloperidol alone (with haloperidol given intravenously). Atypical antipsychotic drugs Olanzapine Olanzapine has been compared with haloperidol in a randomized controlled trial involving 73 patients. Patients satisfying DSM-IV criteria for delirium were randomized to haloperidol or olanzapine and the results showed no difference in the reduction of delirium over time. However, intravenous haloperidol as a rescue drug was used in 36% of those taking olanzapine on the first day of delirium and 18% of patients on the second day; this clearly contaminated interpretation of the findings. No other controlled trials have been carried out with olanzapine but reports suggest that it is efficacious and with few extrapyramidal effects (Sipahimalani & Masand, 1998). Risperidone A randomized double-blind trial of risperidone and haloperidol in the treatment of delirium (Han & Kim, 2004) showed no difference between the two drugs but only 24 patients entered the trial. However, those treated with haloperidol had a 75% response compared with 42% on risperidone. Rather better results have been understandably found in open studies (Horikawa et al., 2003; Parellada et al., 2004). It is difficult to make any firm conclusions about risperidone on the basis of these data. Quetiapine, ziprasidone, and remoxipride Open studies have suggested that these three drugs may have some value in the treatment of delirium (Robertson et al., 1996; Schwartz & Masand, 2000; Kim et al., 2003) but no definite conclusions can be drawn from them. Cholinesterase inhibitors As these drugs are commonly used in the treatment of dementia and
6 Organic disorders behavioural disturbance (see following chapters) it is not surprising that they, mainly donezepil and rivastigmine, have been used in the treatment of delirium. One small trial with 15 patients treated with rivastigmine (1.5 mg increasing to 3.0 mg/ day) showed shorter duration of delirium compared with placebo (Overshott et al., 2010), but another larger trial of rivastigmine 4.5 mg daily versus placebo (Gamberini et al., 2009) showed no benefit for the active drug. Benzodiazepines Although benzodiazepines reduce the risk of extrapyramidal symptoms (Menza et al., 1998) they sometimes promote cognitive impairment. This problem has only been marked in the study by Breitbart et al. (1996), which used high doses. Nevertheless, a recent Cochrane Review concluded no adequately controlled trials could be found to support the use of benzodiazepines in the treatment of nonalcohol withdrawal-related delirium among hospitalized patients, and at this time benzodiazepines cannot be recommended for the control of this condition (Lonergan et al., 2009). Mianserin This atypical antidepressant drug has been compared with haloperidol in 40 patients diagnosed with delirium using DSM-IV criteria (Nakamura et al., 1997). Again there was no difference in the improvement between the groups with 7 out of 10 patients improving on these treatments. Mianserin was given in a dose of between 10 mg and 60 mg a day and caused oversedation in two patients. Electroconvulsive therapy This treatment has been given in the past for delirium but is highly unlikely to be given nowadays. Nevertheless, an old study based on retrospective chart review suggested that patients receiving ECT together with conventional treatment had a shorter duration of delirium symptoms than those just receiving the treatment without ECT (Dudley & Williams, 1972). Guidelines The American Psychiatric Association Practice Guidelines for the Treatment of Patients with Delirium (American Psychiatric Association, 1999) supports the use of antipsychotics as the main pharmacological treatment of choice in delirium. Haloperidol has been identified as the most appropriate and it is suggested that the dosage should be started at 1 2 mg every 2 to 4 hours as needed (with half of this dosage in the elderly) and, when problems become more severe, the
Table 1.1 Evidence base for interventions in delirium Treatment Form of treatment Psychiatric disorder Level of evidence to test efficacy Comments Environmental manipulation of those at risk Typical antipsychotic drugs Haloperidol in oral, intramuscular or intravenous Reorientation procedures Delirium Ib One randomized trial gave form Chlorpromazine Atypical antipsychotic drugs Risperidone Quetiapine Remoxipride Delirium of all types including hypoactive delirium Delirium with or without dementia results supportive of this intervention Ib Effective, but the extrapyramidal and sedative effects may Ib III III preclude use Limited evidence, most favouring risperidone Atypical antipsychotic drugs Olanzapine Delirium of all types III Alleged similar efficacy to Benzodiazepines Lorazepam Delirium of all types Benzodiazepines and antipsychotic drugs but specifically effective in alcohol withdrawal delirium (see p. 52) haloperidol but studies inadequate to confirm Ib Probably effective in lower dosage, but adds to cognitive impairment in higher dosage Haloperidol and lorazepam Delirium III A favoured combination, but no good evidence in support
Table 1.1 (cont.) Treatment Form of treatment Psychiatric disorder Level of evidence to test efficacy Comments Benzodiazepines and opioids Diazepam, flunitrazepam, and pethidine Prevention of postoperative delirium IIb Some evidence of efficacy but needs replication 5-HT 3 receptor antagonists Odansetron Postoperative delirium III Only tested in open study Cholinesterase inhibitors Donepezil Rivastigmine Mixed delirium Ib Two randomized trials of rivastigmine in delirium, one positive (small trial) and the other negative (large trial) Tetracyclic antidepressants Mianserin Delirium of all types IIa May be equivalent in efficacy to haloperidol but limited evidence Psychostimulants Methylphenidate Hypoactive delirium III One study (before after) with limited conclusions Electroconvulsive therapy (ECT) Bilateral Delirium tremens in particular III Case reports only
Delirium 9 drug can be given by intravenous injection of 10 mg followed by intravenous infusion of up to 5 10 mg per hour. However, this is based on only one case series and has come under criticism (Tauscher et al., 2000). The National Institute for Health and Clinical Excellence has also developed a guideline for prevention and treatment and the recommendations for prevention of delirium for patients at risk are to ensure that people at risk of delirium are cared for by a team of healthcare professionals who are familiar with the person at risk (National Clinical Guidance Centre for Acute and Chronic Conditions, 2010). For those diagnosed with delirium the recommendations are to (i) identify and manage the possible underlying cause or combination of causes and (ii) ensure effective communication and reorientation and provide reassurance for people diagnosed with delirium, with family, friends, and carers when available, who may be able to help with this. If these non-pharmacological approaches are ineffective, the guideline suggests the practitioner should consider giving short-term (for 1 week or less) haloperidol or olanzapine. This guideline is not fundamentally different from the American one and does not alter the basic recommendations. Summary Delirium is an acute psychiatric event and it is understandable that there are few randomized controlled trials comparing forms of treatment, and none which includes placebo control. This complicates interpretation of management but there is a large body of data that supports (i) sensitive environmental adjustment and reorientation (for prevention and initial management) and (ii) pharmacological intervention with antipsychotic drugs (for delirium unresponsive to environmental interventions). The other drugs considered for the treatment of delirium are not to be used without very careful consideration after first-line treatments have failed (Table 1.1).
2 Management of behavioural and psychological symptoms of dementia and acquired brain injury Based on Management of behavioural and psychological symptoms of dementia and acquired brain injury by Joel Sadavoy, Krista L. Lanctôt and Shoumitro Deb in Effective Treatments in Psychiatry, Cambridge University Press, 2008 Introduction Some might find the title and terminology of this chapter a little unusual, but it comes from the guidelines of the International Psychogeriatric Association (1998, 2002) which brought together this group of symptoms under the heading of Behavioural and Psychological Symptoms in Dementia (BPSD). Although it is not a diagnostic term it is nonetheless useful when it comes to managing individual patients, as it is the symptoms and manifest behaviour that the clinician is called upon to treat irrespective of their diagnostic background. As often these behaviours are acute in presentation, drug treatment is used most frequently in their management. These disturbances are very common and occur almost always at some point in a long dementing illness. Rubin et al. (1988) describes seven types of these behavioural problems memory disturbance, physical violence and hitting, incontinence, catastrophic reactions, suspiciousness, and accusatory behaviour. These are clearly disturbing symptoms and can often lead to major problems in hospitals, care homes, 10