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EDITORIALS: Rohan Ganguli and Martin Strassnig Are older antipsychotic drugs obsolete? BMJ 2006; 332: 1346-1347 [Full text]

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Truly novel agents are much awaited

arnob chakraborti   (10 June 2006)

Don't forget the depots

James Rucker   (10 June 2006)

Antipsychotics should be drugs of last resort

Bruce G Charlton   (11 June 2006)

Typical antipsychotics are not obsolete, but a shotgun approach to treatment of psychosis should be.

Gabriel A de Erausquin, Julian Bustin and Sergio Strejilevich   (16 June 2006)

Older generation antipsychotic medications are still useful in developing countries

AMIN ALI MUHAMMAD GADIT   (16 June 2006)

Survey Your Patient's Preference Between Older Antipsychotics and the Newer Ones

Babatunde Adetunji, MD, Maju Mathews MD, Biju Basil MD and Oluyemisi Adetunji BA, MS, RN (UK)   (17 June 2006)

All antipsychotics are not equal

Anju Kuruvilla, Suja Kurian, Rajesh Gopalakrishnan, KS Jacob   (26 June 2006)

pregnancy and schizophrenia

Bharathi Balasundaram   (17 November 2006)

Truly novel agents are much awaited 10 June 2006
arnob chakraborti, senior house officer dorothy pattison hospital, walsall PCT, WS2 9XH Send response to journal: Re: Truly novel agents are much awaited	Dear Editor-I would begin with my whole-hearted agreement with the authors on-“Truly novel agents are still needed”. The practise of anti- psychotic prescription in the United Kingdom has come to be based on the guidelines provided by the National Institute for Clinical Excellence (NICE), which were issued in December 2002. The guidelines have stood on a ground of robust evidence base for the day. NICE suggests that for a person who has been newly diagnosed with schizophrenia, doctors should consider prescribing one of the following atypical (newer) oral antipsychotic drugs: amisulpride, olanzapine, quetiapine, risperidone or zotepine.1. And for people who are currently taking typical (older) antipsychotic drugs that are controlling their symptoms of schizophrenia but are causing side effects that and the individual and doctor agree are unacceptable, the doctor should consider prescribing an oral atypical antipsychotic (amisulpride, olanzapine, quetiapine, risperidone, sertindole or zotepine).1. NICE does not recommend that people with schizophrenia should change to one of the atypical (newer) antipsychotic drugs if they are currently taking typical (older) anti-psychotics that are controlling the symptoms of schizophrenia and are not causing unacceptable side effects. 1. Atypical and typical antipsychotic drugs should not be prescribed at the same time except for short periods if patients are changing drugs. 1. TRS (Treatment Resistant Schizophrenia) is suggested by a lack of satisfactory clinical improvement despite the sequential use of the recommended doses for 6 to 8 weeks of at least two anti-psychotics, at least one of which should be an atypical. 1. Whilst the general observation in clinical practise is that a new diagnosis of Schizophrenia (or for that matter psychosis) is quickly initiated on an atypical, the diagnosis of TRS comes at a far later stage than the 4 months of a lack of satisfactory response, or for that matter up to 6 months if we add in the time taken for medication change and initial acute stage. This seems to be a preferred and a peer approved practise. The result being a delay in the prescription of Clozapine, which is most likely to be effective. It needs to be ascertained how and why clinicians adhere to the treatment guidance in the first place and then do not follow it down the algorithm. Interestingly, the authors talk about older anti-psychotics not becoming obsolete in clinical practise, while, the amount of research that is conducted solely into their efficacy is pretty slim. Even the researches mentioned by the authors had a single “representative” typical anti-psychotic in and as an arm of the study. We remain in the dark when it comes to comparison between typical anti-psychotics, individualising it to the needs of a patient. The evidence base is anecdotal. In reality, they are very effective in clinical practise, every psychiatrist has a cohort of patients stabilised on them, followed up regularly and maintained similarly lest they should decompensate. However, the giants of the pharmaceutical industry pour funds into development of newer compounds or newer licences for existing “novel anti-psychotics”, and the older ones fade into the background serving mainly as adjuvant to the control of behavioural symptoms on the inpatient unit. We are still to witness a phoenix rising from the ashes. In today’s climate, when the metabolic syndrome, glucose metabolism abnormalities and accelerated aging has been documented with the newer agents and the UK Committee of Safety of Medicines (CSM) informing clinicians that risperidone and olanzapine should not be used to treat behavioural and psychological symptoms of dementia (BPSD) because of increased risk of strokes with both drugs and increased risk of mortality with olanzapine (March 2004), safer avenues of anti-psychotic prescription need to be explored. Baldessarini et al (1988) concluded that moderate doses of chlorpromazine were most effective for acute symptom control, suggesting evidence of a biphasic or inverted-U shaped curve for dose- response relationship. 2. They and others have demonstrated similar results for maintenance therapy. Higher doses merely increase the side- effect burden. The time trusted medications do have a scope, provided they can be supported with a better evidence base into their efficacy and also into their side-effects; a better understanding and openness of ideas. 1.Schizophrenia: NICE guideline, 4 December 2002. 2.Baldessarini RJ, Cohen BM, Teicher MH 1988 Significance of neuroleptic dose and plasma level in the pharmacological treatment of psychoses, Archives of General Psychiatry. Competing interests: None declared
Don't forget the depots 10 June 2006
James Rucker, SHO in Psychiatry South London and Maudsley Rotation Send response to journal: Re: Don't forget the depots	Whilst agreeing with Prof Ganguli, we should also recognise the role of the depot typical antipsychotics. Robert and Geppert pointed out the association of typical depot antipsychotics with improved global outcome and reduced risk of rehospitalisation, a reduced burden of care as well as more predictable bioavailability (Robert & Geppert, 2004). The only atypical depot currently available (Risperidone Long Acting Injection) is very expensive and, I am repeatedly told by my patients, extremely painful to have. Its efficacy has also not been compared to typical depots in robust trials. A depot version of Olanzapine (Olanzapine Pamoate) is currently in phase 3 trials however this will doubtless be, on the assumption it is ever released, at least as expensive as depot Risperidone with an unknown safety profile and efficacy record. Whilst the oral typical antipsychotics are still of clinical use, the depot typical antipsychotics are still clinically essential. Competing interests: None declared
Antipsychotics should be drugs of last resort 11 June 2006
Bruce G Charlton, Reader in Evolutionary Psychiatry University of Newcastle upon Tyne, NE1 7RU, UK Send response to journal: Re: Antipsychotics should be drugs of last resort	Antipsychotics (aka neuroleptics) are probably the most loathed of all medications among psychiatric patients. The failure of ‘atypical’ agents to improve on older drugs invites reconsideration of the therapeutic validity of this whole class [1]. Short-term effectiveness is not in doubt, but in the long-term antipsychotics cause more problems than they solve [2]. Parkinsonism is inevitable, including not just the motor pathology but more insidiously- damaging psychological symptoms of emotional-blunting, anhedonia and demotivation [1, 3]. Problems such as physical dependence, hypersensitivity phenomena and withdrawal-induced exacerbations may explain why schizophrenic patients have a better prognosis in countries that do not use neuroleptics [2]. There are safer and less unpleasant alternatives for many patients and situations, including sedatives or ECT for acute psychotic agitation [1, 4] and early treatment of symptom exacerbations using diazepam [5]. The lesson of fifty years is that most patients would be better-off if neuroleptics had never been invented [1, 2]. References 1. Charlton BG. Why are doctors still prescribing neuroleptics? QJM 2006; 99: 417-20. 2. Whitaker R. The case against antipsychotic drugs: a fifty year record of doing more harm than good. Medical Hypotheses 2004; 62: 5-13. 3. Healy D. The creation of psychopharmacology. Harvard, MA, USA: Harvard Univesrity Press, 2002. 4. Small JG, Klapper MH, Kellams JJ, Miller MJ, Milstein V, Sharpley PH, Small IF. ECT compared with lithium in the management of manic states. Archives of General Psychiatry 1988; 45: 727-32. 5. Carpenter WT, Buchanan RW, Kirkpatrick B, Brier AF. Diazepam treatment of early signs of exacerbation in schizophrenia. American Journal of Psychiatry 1999; 156: 299-303. Competing interests: None declared
Typical antipsychotics are not obsolete, but a shotgun approach to treatment of psychosis should be. 16 June 2006
Gabriel A de Erausquin, Assistant Professor of Psychiatry and Neurology. Washington University School of Medicine (63110), Julian Bustin and Sergio Strejilevich Send response to journal: Re: Typical antipsychotics are not obsolete, but a shotgun approach to treatment of psychosis should be.	Dear Editor. We read with great interest the editorial by Professor Ranguli and Dr Strassnig regarding the usefulness of older antipsychotic drugs. The editorial serves as a useful guide for clinicians in search of the appropriate drug for their patients suffering from psychosis. We would like to contribute to the discussion by adding a consideration seldom mentioned when discussing the pros and cons of pharmacological treatment of schizophrenia. Not all patients sharing a diagnosis have the same clinical characteristics. Since currently no disease-modifying treatments are available for schizophrenia, different clinical manifestations should call for different symptomatic treatments. We recently published a study comparing patients with schizophrenia who became stable on typical antipsychotic drugs with those did so on clozapine(1). We did not find any significant difference between the two groups either in terms of symptom severity or in quality of life, but did find that susceptibility to extrapyramidal side-effects (EPS) could explain why they responded differently to different drugs . In particular, those patients with greater sensitivity to EPS became stable on clozapine, yet had comparable residual symptoms and quality of life to patients who had tolerated typical antipsychotics, which are more affordable and have fewer adverse metabolic effects. Thus, early identification of sensitivity to EPS in patients with schizophrenia could save costs and reduce metabolic risk without sacrificing symptomatic relief or quality of life. This line of reasoning may not be limited to the treatment of schizophrenia. For instance, the use of psychotropic medications in the elderly is ridden with questions begging to be addressed, including but not limited to the advantage of specific mood stabilisers (2), or the increased risk of death with atypical antipsychotics (3), or suicide with SSRI (4). There can be no doubt that the new psychotropic drugs have improved the treatment of some psychiatric patients. Yet given the high costs and attendant risk of metabolic syndrome associated with these drugs, identifying those persons most likely to benefit from their use should be a priority. The idea of "one-size-fits-all" treatmet of psychotic symptoms should soon be obsolete with the help of finer identification of individual susceptibilities, including that afforded by pharmacogenetics. Dr Julian Bustin Staff Grade in Old Age Psychiatry St Pancras Hospital, London, UK Sergio Strejilevich Director "ÁREA", Investigación y Desarrollos en Neurociencias Clínicas Reseacher in schizophrenia and neurodevelopment. Gurruchaga 2463 1º C (1425) Ciudad de Buenos Aires Argentina 4833-2424 sstreji@arnet.com.ar Gabriel A. de Erausquin, MD, PhD Assistant Professor of Psychiatry and Neurology. Researcher in schizophrenia and neurodevelopment. Washington University School of Medicine 1) Strejilevich SA, Palatnik A, Avila R, Bustin J, Cassone J, Figueroa S, Gimenez M, de Erausquin GA. Lack of extrapyramidal side effects predicts quality of life in outpatients treated with clozapine or with typical antipsychotics.Psychiatry Res. 2005 Feb 28;133(2-3):277-80. 2)Shulman KI, Rochon P, Sykora K, Anderson G, Mamdani M, Bronskill S, Tran CT. Changing prescription patterns for lithium and valproic acid in old age: shifting practice without evidence. BMJ. 2003 May 3;326(7396):960-1. 3) Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry. 2006 Mar;14(3):191-210. 4)Juurlink DN, Mamdani MM, Kopp A, Redelmeier DA. The risk of suicide with selective serotonin reuptake inhibitors in the elderly.Am J Psychiatry. 2006 May;163(5):813-21. Competing interests: SS received fees for speaking from several pharmaceuticals companies. These companies did not provide funding for the current letter or study cited
Older generation antipsychotic medications are still useful in developing countries 16 June 2006
AMIN ALI MUHAMMAD GADIT, Professor of Psychiatry Memorial University of Newfoundland, St. John's, A1B 3V6, Canada Send response to journal: Re: Older generation antipsychotic medications are still useful in developing countries	The psychiatric treatment has been revolutionized by the introduction of new generation antipsychotics but the older generation drugs are still very useful for developing countries like Pakistan where the health care services are available through out-of-pocket expenses and the exorbitant cost of these novel medications are most of the time beyond the reach of ordinary people. In many underprivileged areas of the country, these drugs are used liberally and are also found to be effective. In order to give the benefits of newer drugs, their cost has to reduced significantly and this does not appear to be possible in the foreseeable future. Competing interests: None declared
Survey Your Patient's Preference Between Older Antipsychotics and the Newer Ones 17 June 2006
Babatunde Adetunji, MD, Clinical Assistant Professor of Psychiatry, Drexel University College of Medicine, Philadelphia, USA MHM Services, MOD-2, 8001 State Road, Philadelphia, USA, Maju Mathews MD, Biju Basil MD and Oluyemisi Adetunji BA, MS, RN (UK) Send response to journal: Re: Survey Your Patient's Preference Between Older Antipsychotics and the Newer Ones	After reading Professor Ganguly and Dr Strassnig’s article (1), and based on research studies and our clinical experiences, we would like psychiatrists to provide the following comparisons to their patients and discover which group of medications they would choose: Efficacy: Older Antipsychotics are equal to the newer antipsychotics (2) Side effects: Diabetes, Weight gain,Hypertension and hyperlipidemic propensity of new antipsychotics versus movement disorders of older antipsychotics. Costs: Incomparably cheaper older antipsychotics versus expensive second generation antipsychotics (3) As soon as we mention the components of metabolic syndrome above, most of our patients have been preferring the older medications, especially at lower doses. Our conclusion converges with those of Professor Ganguly and Dr Strassnig that these medications are not obsolete. We believe that their popularity is being drowned out by aggressive marketing strategies of the manufacturers of the second generation medications. References 1) Ganguli R and Strassnig M: Are older antipsychotics obsolete? BMJ 2006;332:1346-1347 (10 June) 2) Lieberman JA, Stroup TS, McEvoy JP et al. For the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005;353: 1209-23 3) Biju Basil, Maju Mathews, Babatunde Adetunji, & Kumar Budur: Cost of the CATIE Study’s Antipsychotic Medications at a Chain Pharmacy. American Journal of Psychiatry, 163(3)555. March 2006. Competing interests: None declared
All antipsychotics are not equal 26 June 2006
Anju Kuruvilla, Reader Department of Psychiatry, Christian Medical College, Vellore, India-632002, Suja Kurian, Rajesh Gopalakrishnan, KS Jacob Send response to journal: Re: All antipsychotics are not equal	We read the editorial titled ‘Are older antipsychotic drugs obsolete?’ 1 with interest. The older, typical antipsychotics are regularly used in India as first and second line treatments alongside the newer atypical drugs which are also freely available. Many factors are taken into account while deciding on which antipsychotic is best suited for an individual patient. Since the efficacy of all the antipsychotics (excluding clozapine) are equal, the decision regarding which drug is to be started is usually based on the match between side-effect profile of the drug and clinical characteristics of the patient. Sedative antipsychotics are preferred in patients who are agitated (E.g. chlorpromazine, olanzapine). Olanzapine and quetiapine are avoided for patients with obesity, a personal or family history of diabetes. Patients with a history of transient ischaemic attacks or stroke also require the avoidance of risperidone and olanzapine. Typical agents are preferred in such cases. Although described to have less side-effects and therefore better tolerability, the atypical antipsychotics often have distressing side- effects similar to the typicals, especially when prescribed in higher doses. For example, akathisia with risperidone and olanzapine and extra- pyramidal symptoms and tardive dyskinesia with risperidone are commonly encountered. Sexual side-effects are also frequently experienced with both these groups of drugs. Financial considerations also determine the choice of antipsychotic as most people do not have health insurance and have to pay for treatment. The more expensive atypicals also have the extra costs related to the monitoring for metabolic side-effects. The conventional drugs though cheaper, may lose that advantage in higher doses as they have to be combined with anticholinergic agents used to reduce their extrapyramidal symptoms. Typical antipsychotic depots are more commonly employed compared to atypical long acting preparations due to their reduced costs. It is clear that antipsychotics are not equal. Treatment decisions, therefore, need to be based on clinical profiles of patients and the risk and benefits of the different antipsychotic medication. Reference: 1. Ganguli R, Strassnig M. Are older antipsychotic drugs obsolete? BMJ 2006; 332: 1346 – 1347. Competing interests: None declared
pregnancy and schizophrenia 17 November 2006
Bharathi Balasundaram, specialist registrar old age psychiatry,Leeds mental health trust ,Leeds Ls14 1PP Send response to journal: Re: pregnancy and schizophrenia	Dear editor I fully concur with professor Ganguli's editorial that older antipsychotics have not become obsolete. I would like to discuss about pregnancy in people with schizophrenia,a vulnerable group of patients. Pregnancy is a life event which can provoke worsening of mental status especially in younger woman with unwanted pregnancies.The safety of psychotropic medication cannot be clearly established because robust, prospective trials are obviously unethical.If drug treatment in pregnancy is considered,older medications such as chlorpromazine,trifluoperazine are recommended as more clinical experience has accumulated with these drugs than the newer ,novel atypical antipsychotic medications.Inaddition older drugs are generally considered to have minimal risk of teratogenicity. Data on some atypicals are now emerging.Clozapine is not known to be associated with teratogenicity but may pose extra risks in pregnancy given the inability to monitor fetal hematology. Not all authorities agree that olanzapine is likely to be free of teratogenicity. Gestational diabetes is associated with both clozapine and olanzapine. Psychiatrists should make an individualised assessment of risks and benefits of antipychotic medications,discuss with patients risks versus benefits, document all decisions, should not hesitate to seek advice from manufacturers, pharmacists and other specialists. Older antipsychotics clearly have a role in this vulnerable group. references 1.Taylor D,Paton C,Kerwin R,The Maudsley prescribing guidelines 2005- 2006 8th edition. 2.Altshuler LL, Cohen L,Szuba MP et al,Pharmacological management of psychiatric illness during pregnancy:dilemmas and guidelines,Am J Psych (1996) 153:592-606. Patton SW,Misri S,Corral MR et al.Antipsychotic medication during pregnancy and lactation:evaluating the risk . Can J Psychiatry 2003; 47:959-965 Competing interests: None declared