GUIDELINES FOR THE USE OF PSYCHOSTIMULANTS IN PALLIATIVE CARE

Transcription

1 GUIDELINES FOR THE USE OF PSYCHOSTIMULANTS IN PALLIATIVE CARE 36.1 GENERAL PRINCIPLES Current research evidence supports the use of psychostimulants in palliative care in four areas: depression; 1, 2 opioid induced sedation; 3, 4 hypoactive delirium 5 and cancer-related fatigue. 6 They are not appropriate for use as day time stimulants in the palliative care setting. 7 A psychostimulants may be the drug of choice for treating depression in patients with a prognosis of < 3 months because they may not live long enough to achieve maximum benefit from a conventional antidepressant. However they are not as effective as conventional 1, 2, 8 antidepressants which should be considered in patients with a prognosis of > 3 months. The most commonly used psychostimulant in palliative care is methylphenidate hydrochloride. It has been shown to be effective in the management of cancer related fatigue 6. Dexamfetamine (Dexedrine ) and modafinil (Provigil 9, 10, 11 ) are alternatives. Psychostimulants (with the exception of modafinil) are Schedule 2 drugs, and therefore are subject to the regulations for controlled drugs. Prescriptions must comply with controlled drug requirements. 7 The UK product licences do not currently cover the use of these psychostimulants in palliative care. Methylphenidate hydrochloride increases dopamine signalling by several mechanisms including blocking the dopamine re-uptake transporter, and modulates catecholamine tone. 12 Methylphenidate hydrochloride is available in both short acting and long acting formulations. The long acting formulations should be avoided for palliative care use. Tablets may be dispersed in water (allow 2-5 minutes) and dispersed tablets may be administered via a PEG tube. 13 Methylphenidate hydrochloride is rapidly and completely absorbed after oral administration, reaching peak blood levels in 1-3 hours. 7 A test dose of 5mg methylphenidate hydrochloride should always be tried before commencing any treatment regimen. In the frail or elderly a starting dose of 2.5mg may be more 5, 14 appropriate. Care should be taken when prescribing psychostimulants in patients with marked anxiety, agitation, hypertension or epilepsy. They should be discontinued if seizures occur, there is a rise in blood pressure or an increase in anxiety or agitation. 13 6, 10 Methylphenidate hydrochloride is generally well tolerated in the palliative care population. Serious side effects such as aggression or psychosis have been reported in 2-4 % of patients following a test dose of psychostimulants. 4 A past history of aggression or psychosis was a common feature in many of these patients. Stopping the psychostimulants and use of haloperidol is often helpful. The most commonly reported side effects are insomnia, anorexia, irritability, weight loss, abdominal pain and headaches. 13 Psychostimulants may also cause tachycardia and hypertension. 7 Stimulant side effects tend to be dose-dependent. Despite the potential negative

2 impact on appetite, anxiety and insomnia, when used in the palliative care population the increased arousal and improved mood often negates these effects or even reverses them. 15 Absolute contraindications to the use of psychostimulants include hyperthyroidism, angina, severe hypertension, glaucoma, schizophrenia and cardiac arrhythmias. Relative contraindications are mild hypertension, Tourette s syndrome, motor tics, drug abuse, alcohol 7, 15 abuse, porphyria and epilepsy. Psychostimulants have several potentially important drug interactions. (see Table 36.1) Table 36.1 Important drug interactions of methylphenidate hydrochloride 7 Drug(s) Phenytoin Phenobarbital Primidone Carbamazepine All antihypertensives MAOI* Moclobemide* Alcohol Warfarin Tricycyclic antidepressants SSRIs Effect Increase plasma levels of anticonvulsants. Effectiveness of methylphenidate may be reduced. Monitor effect. Antagonises hypotensive effects. Increases hypertension and CNS excitation. * There is a risk of a hypertensive crisis and psychostimulants should not be used either with, or within 14 days, of administering MAOIs. Use with caution with drugs that are predominantly metabolised by CYP2D6 e.g. warfarin, as a degree of competitive inhibition may develop. Serious adverse events have been reported with clonidine, but a causal relationship has not been established. 8 Concurrent use of anti-dopaminergic agents such as haloperidol, levomepromazine and metoclopramide may reduce the clinical response to psychostimulants with the exception of modafinil. 7, GUIDELINES Table 36.2 describes the clinical use of psychostimulants in palliative care STANDARDS 1. All patients should receive a test dose of the psychostimulant before commencing a treatment regimen. 14 [Grade D] 2. Pulse rate and blood pressure should be monitored on a daily basis during the titration phase. 7 [Grade D] 3. The clinical response to psychostimulants should be closely monitored and recorded in the case notes. 2 [Grade D] 4. If a patient is discharged on psychostimulants, a copy of the discharge letter should be sent to the GP and other health professionals involved in their care. 2 [Grade D]

3 Table 36.2 Clinical use of methylphenidate hydrochloride, dexamfetamine and modafinil 7, 8 [Level 3] Indication Dosing regimen Response Long term use 1. Diagnosis of depression and/or adjustment disorder using ICD 10 or DSM IV (see Guidelines on Depression). 2. Where a rapid response is required (prognosis less than 3 months) and/or other antidepressants are contraindicated or not tolerated. Cancer-related fatigue. Opioid induced sedation. Methylphenidate hydrochloride Initial test dose of 5mg methylphenidate hydrochloride. Monitor closely for any adverse reactions. In the frail or elderly it may be more appropriate to use a starting dose of 2.5mg methylphenidate hydrochloride. Following test dose, use methylphenidate hydrochloride 5mg bd. Do not give second dose later than 2pm as may result in sleep disturbance. Titrate upwards as necessary by 2.5mg-5mg every hours. During the titration phase, BP and pulse should be monitored on a daily basis. Recommended maximum dose of methylphenidate hydrochloride is 40mg/day. 5 If no response and treatment is still indicated, consider changing to dexamfetamine sulphate. Dexamfetamine Can be given once daily 2.5mg- 5mg od as starting dose. Can increase every few days to 20mg od depending on response. Monitor as above. Modafinil dose 100mg (elderly)-200mg (adult) per day orally as single morning dose. Adjust according to response to a maximum of 400mg daily. Monitor as above. As above. As above. A response occurs within 48 hours in 75% of patients. The response rate may be less in those with a shorter prognosis. Important to monitor. Important to monitor. Long term use (up to 12 months) has been observed. Stopping treatment may lead to withdrawal symptoms and a reducing regimen is recommended. Depression may recur once treatment is discontinued. Tolerance to methylphenidate hydrochloride is more likely to develop if used for > 4 weeks. 8, 13

4 36.4 REFERENCES 1. Macleod AD. Methylphenidate in terminal depression. J Pain Symptom Manage 1998; 16(3): Merseyside and Cheshire Palliative Care Network Audit Group. Use of Psychostimulants in Palliative Care. Expert Consensus. September Bruera E, Miller MJ, Macmillan K, Kuehn N. Neuropsychological effects of methylphenidate in patients receiving a continuous infusion of narcotics for cancer pain. Pain 1992; 48(2): Bruera E, Brenneis C, Paterson AH, MacDonald RN. Use of methylphenidate as an adjuvant to narcotic analgesics in patients with advanced cancer. J Pain Symptom Manage 1989; 4(1): Gagnon B, Low G, Schreier G. Methylphenidate hydrochloride improves cognitive function in patients with advanced cancer and hypoactive delirium: a prospective clinical study. J Psychiatry Neurosci. 2005; 30(2): Minton O, Stone P, Richardson A, Sharpe M, Hotopf MM. Drug Therapy for the Management of Cancer Related Fatigue. The Cochrane Database of Systematic Reviews 2008 Issue 1. Art No: CD DOI / CD Twycross R, Wilcock A. (editors) Palliative Care Formulary. 3rd edition. Nottingham Palliativedrugs.com Ltd p Candy B, Jones L, Williams R, Tookman A, King M. Psychostimulants for depression. Cochrane Database of Systematic Reviews Issue 2. Art No. CD DOI / CD pub Auret KA, Schug SA, Bremner AP, Bulsara M. A randomized, double-blind, placebocontrolled trial assessing the impact of dexamfetamine on fatigue in patients with advanced cancer. J Pain Symptom Manage 2009; 37(4): Breitbart W, Alici-Evcimen Y. Update on psychotropic medications for cancer-related fatigue. J Natl Compr Canc Netw 2007; 5(10): Prommer E. Modafinil: Is it ready for prime time? J Opioid Manage 2006; 2(3): Wilens TE. The effects of methylphenidate on the catecholaminergic system in attentiondeficit/hyperactivity disorder. J Clin Psychopharmcol 2008; 3(Suppl 2): Joint Formulary Committee. British National Formulary 58, London: British Medical Association and Royal Pharmaceutical Society of Great Britain, Kurscheidt JC, Peiler P, Behnken A, Abel S, Pedersen A, Suslow T et al. Acute effects of methylphenidate on neuropsychological parameters in adults with ADHD: Possible relevance for therapy. J Neural Transm. 2008; 115(2): Bruera E, Driver L, Barnes EA, Willey J, Shen L, Palmer JL et al. Patient-controlled methylphenidate for the management of fatigue in patients with advanced cancer: a preliminary report. J Clin Oncol 2003; 21(23):

5 36.5 CONTRIBUTORS Lead Contributors Dr J Skinner Macmillan Consultant in Palliative Medicine County Durham Primary Care Trust Dr A Murray Staff Grade Physician St Catherine s Hospice Preston External Reviewer Dr T Rimmer Macmillan Consultant in Palliative Medicine/Medical Director East Cheshire Hospice Macclesfield