Choice of Antipsychotic Medication

Transcription

1 Choice of Antipsychotic Medication Schizophrenia is a condition with profound consequences for the affected person, their social environment and society as a whole. The gravity of the condition is reflected in total yearly per capita Health and Social Care costs which have been estimated to be approximately 38,000 at 2006 prices (Mangalor & Knapp, ). Of these direct costs 1.6% is attributable to the cost of pharmacotherapy. The average cost of a relapse event in schizophrenia has been estimated to be approximately 25,000 (Munro et al, ). From the point of onset, schizophrenia is a relapsing disorder in the vast majority of patients: If followed up from the first presentation more than 95% of patients will have suffered relapse by 5 years. (Robinson et al, ). Thus, a central therapeutic enterprise in schizophrenia is to establish the patient in maintenance, relapse preventative, pharmacotherapy. Antipsychotic drugs are of indisputable value in preventing relapse of schizophrenia. Although different studies give somewhat varying figures the overall effect of maintenance antipsychotic pharmacotherapy is to reduce annual relapse rates to about half of what they would have otherwise been without treatment. Typical figures are that 50% of schizophrenia cases would relapse each year without treatment, but only 25% would do so with treatment (Dellva et al 1997, Pigott et al ). Thus, of all modern healthcare interventions the maintenance pharmacotherapy of schizophrenia stands among the most effective. However, this optimistic account is tempered by the observation that antipsychotic drugs, as a class, have poor tolerability, safety and acceptability for patients. For example, in the well-known CATIE study (Lieberman et al ) 74% of cases discontinued their selected antipsychotic pharmacotherapy within 18-months of initiation, with subsequent high exposure to relapse and its consequences. Although intolerability of treatment 1 Cost of Schizophrenia in England, Roshni Mangalore and Martin Knapp. PSSRU Discussion Paper. October Hospital treatment and management in relapse of schizophrenia in the UK: associated costs.) Janet Munro,Sarah Osborne, Lindsay Dearden. and Katie Pascoe, Aline Gauthier, Martin Price. The Psychiatrist Online March : Robinson et al Arch Gen Psychiatry. 1999;56: Psychiatr Serv Dec;48(12): J Clin Psychiatry Sep;64(9): N Engl J Med 2005;353: Page 1 of 7

2 due to specific adverse effects was a significant factor in ceasing treatment (about one-third of discontinuations) a greater effect of patient preference was seen, with half of all discontinuations being attributable to patient decision. It is evident, therefore, that acceptability of treatment is a pivotal factor for the patients and exerts more influence than side effects of treatment as judged clinically. Antipsychotic drugs differ markedly in their individual pharmacology and do not have a uniform class pharmacology such as is found with SSRI antidepressants or statins. The comparisons and contrasts are many but examples would include the following: Olanzapine is characterized by being calming and anxiolytic but at the expense of sedation and severe weight gain; risperidone, by contrast, is non-sedative and not greatly prone to cause metabolic disorder but incurs the common penalties of Parkinsonian movement disorder and hyperprolactinaemia; aripiprazole is resilient against non-compliance by virtue of its extremely long half-life but is associated with insomnia and akathisia. Thus a central focus in the doctor-patient relationship around the long-term management of schizophrenia is selecting, and settling on, a treatment option that offers the best compromise for the patient in terms of effectiveness and acceptability. This is not necessarily achieved quickly and may involve many revisions of treatment over the early years of the illness until the most satisfactory, or least unsatisfactory, is found. But a central characteristic of this process is that the patient has, in effect, the final say: If the treatment is not acceptable to them, individually, they can exercise the option to take no treatment at all with undesirable consequences for all concerned. It is therefore unsurprising that senior psychiatrists make the case that seeking the treatment for each patient that is both optimized and individualized requires access to a full range of therapeutic options. We have considerable sympathy with such opinion and accept that constraints on treatment options can certainly not improve the overall acceptability of antipsychotic treatment and that the costs, personal, societal and heatheconomic of even marginally less acceptable treatment could be substantial. Achieving the most cost efficient use of antipsychotic drugs may be a stretching matter even for the most senior psychiatrists but until such time as there is more formal empirical evidence, or advances in therapy, we are substantially reliant on clinical expertise as the most significant guiding factor. Page 2 of 7

3 Care Quality Commission Standards Outcome 9 (Regulation 13): Management of Medicines 9a Providing personalised care through the effective use of medicines Provide evidence to demonstrate that people who use services receive medicines which are deemed appropriate for them as individuals. People who use services receive care, treatment and support that ensures the medicines given are appropriate and person-centred by taking account of their: age choices lifestyle cultural and religious beliefs allergies and intolerances existing medical conditions and prescriptions adverse drug reactions recommended prescribing regimes. Ensures the person s prescription for medicines, for which the service is responsible, is up to date and is reviewed and changed as their needs or condition changes. Includes monitoring the effect of their medicines and action when necessary if their condition changes, including side effects and adverse reactions. Page 3 of 7

4 Drug Adult max dose Elderly max dose Antipsychotics Relative side-effects Anticholinergic Relative side-effects (most will be dose related) Sedation Minor O/D Weight gain Prolactin Phenothiazines Chlorpromazine 1000 <Ad? Levomepromazine 1000 NR???? (methotrimeprazine) Promazine 800 <Ad??? Pericyazine (300) <Ad??? Thioridazine 600 <Ad?? Fluphenazine CA20 CA10? Perphenazine 24 <Ad O?? Trifluoperazine - <Ad?? Others Benperidol 1.5 <Ad??????? Haloperidol 30 30? Flupentixol 18 <Ad O O?? Zuclopenthixol 150 <Ad?? O? Pimozide 20 <Ad O? Amisulpride O O O O? Sulpiride O O O? Depot and long-acting injections 1 Fluphenazine Pipotiazine palmitate Haloperidol Flupentixol 100-2/52 <Ad? 200-4/52 <Ad O???? 300-4/52 <Ad 400-1/52 <Ad O O??? Cardiac EPSE Hypotension Proconvulsant Page 4 of 7

5 Drug Adult Elderly Relative side-effects (most will be dose related) max dose max dose Anticholinergic Cardiac EPSE Hypotension Sedation Minor O/D Weight gain Prolactin Proconvulsant Zuclopentixol 600-1/52 <Ad?? O? Fluspirilene 20-1/52 <Ad??? Risperidone Consta 50-2/ /52 O O?? O Olanzapine pamoate 300-2/52 See SPC O O O O Paliperidone palmitate 150/month Same (ut see SmPC) O O O O Second generation/atypicals Aripiprazole O O O O? O O Asenapine (U, (10) (20) O????????? TBC) Clozapine 900 (900) O? O Olanzapine O O O O Paliperidone O O O O Quetiapine 800 <Ad O Risperidone (16) 4 O O?? O Sertindole (20) (20) O O O O O O Zotepine ??? Ziprasidone (U) - - O O O O? O O O Marked effect O Little or minimal effect Moderate effect? No information or little reported Mild/transient effect U Unlicensed in UK at time of writing Adult max dose Maximum adult oral antipsychotic dose as stated in UK SPC or BNF. May be different for other indications. Elderly max dose Maximum oral antipsychotic dose in the elderly as stated in UK SPC or BNF. Most state that a starting dose of half to a quarter of the adult dose should be adequate, with smaller dose increments /52 mean 100 mg every two weeks; 400-1/52 means 400 mg every week, etc. Reference Stephen Bazire Psychotropic Directory 2012 Page 5 of 7

6 Antipsychotics - Comparative costs for 28 days treatment on maximum doses (Drug Tariff August 2012) (NB Doses quoted do not imply equivalence) Sulpiride tabs 2400ay Sulpiride tabs (Dolmatil) 2400ay Clozapine tabs (Denzapine) 900ay Paliperidone tabs 9ay (Not Approved) Risperidone oral sol 16ml/day Risperidone tabs 16ay Risperdal liquid 16ml/day Risperdal quicklets 16ay Risperdal tabs 16ay Quetiapine tabs 750ay Quetiapine tabs (Gen) 750ay Olanzapine Oro SF (Gen) 20ay Olanzapine Oro (Gen) 20ay Olanzapine velotabs (Zyprexa) 20ay Olanzapine tabs (Zyprexa) 20ay Olanzapine tabs (Gen) 20ay Aripiprazole liquid 30ml/day Aripiprazole oro tabs 30ay Aripiprazole tabs 30ay Amisulpride liq 12ml/day Amisulpride (Solian) 1200ay Amisulpride 1200ay Cost in for 28 days treatment Page 6 of 7

7 Antipsychotic LA & Depot medication Comparative costs for 28 days treatment on ranging doses (Drug Tariff August 2012) (NB Doses quoted do not imply equivalance) Haloperidol (Haldol) 300mg/4w Haloperidol (Haldol) 50mg/4w Pipotiazine (Piportil) 200mg/4w Pipotiazine (Piportil) 100mg/4w Pipotiazine (Piportil) 50mg/4w Fluphenazine (Modecate) 100mg/2w Flupentixol (Depixol Conc) 300mg/2w Flupentixol (Depixol Conc) 50mg/4w Flupentixol (Depixol) 40mg/2w Flupentixol (Depixol) 20mg/2w Zuclopenthixol (Clopixol) 600mg/1w Zuclopenthixol (Clopixol) 500mg/2w Zuclopenthixol (Clopixol) 200mg/2w Risperidone Consta 50mg/2w Risperidone Consta 37.5mg/2w Risperidone Consta 25mg/2w Olanzapine (Zypadhera) 405mg/4w Olanzapine (Zypadhera) 300mg/4w Olanzapine (Zypadhera) 300mg/2w Olanzapine (Zypadhera) 210mg/2w Paliperidone 150mg/4w Paliperidone 75mg/4w Cost in per 28 days Page 7 of 7