Hostname: page-component-586b7cd67f-vdxz6 Total loading time: 0 Render date: 2024-11-22T07:36:06.411Z Has data issue: false hasContentIssue false

Antipsychotic long-acting injections: Mind the gap

Published online by Cambridge University Press:  02 January 2018

Maxine X. Patel*
Affiliation:
Division of Psychological Medicine, Institute of Psychiatry, King's College London
Mark Taylor
Affiliation:
Ballenden House, Edinburgh
Anthony S. David
Affiliation:
Division of Psychological Medicine, Institute of Psychiatry, King's College London, UK
*
Dr Maxine Patel, Division of Psychological Medicine, Box 68, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. Email: [email protected]
Rights & Permissions [Opens in a new window]

Summary

Long-acting injections of antipsychotic medication (or depots) were developed specifically to promote treatment adherence and are a valuable option for maintenance medication in psychotic illnesses. Approximately 40–60% of patients with schizophrenia are partially or totally non-adherent to their antipsychotic regimen, but only 30% or less are prescribed a long-acting injection. The use of such injections has declined in recent years after the introduction of second-generation (atypical) oral antipsychotic drugs. Research shows that possible reasons for this decline include concerns that may be based on suboptimal knowledge, as well as an erroneous assumption that one's own patient group is more adherent than those of one's colleagues. Research on attitudes has also revealed that psychiatrists feel that long-acting injections have an ‘image’ problem. This editorial addresses the gaps in knowledge and behaviour associated with possible underutilisation of these formulations, highlighting the role of stigma and the need for more research.

Type
Editorials
Copyright
Copyright © Royal College of Psychiatrists, 2009 

First-generation antipsychotic (FGA) long-acting injections or depots were developed in the 1960s and were specifically aimed at promoting treatment adherence in people with chronic schizophrenia, thereby enhancing relapse prevention. Reference Davis, Matalon, Watanabe and Blake1Reference Haddad, Taylor and Niaz4 Most patients with schizophrenia (about 80%) recover from their first episode of illness. Of these, approximately 80% then go on to relapse within 5 years. Reference Robinson, Woerner, Alvir, Bilder, Goldman and Geisler5,Reference Barnes, Shingleton-Smith and Paton6 Worse still, approximately 5–10% of people with schizophrenia are thought to complete suicide. Reference Miles7,Reference Palmer, Pankratz and Bostwick8

It is timely to examine the issues around the use of long-acting injections (LAIs) in the maintenance treatment of schizophrenia, as we now have sufficient experience of the first second-generation antipsychotic LAI – risperidone LAI – which has been available since 2002. Another second-generation LAI has been licensed and a third is in process. Reference Fleischhacker9 This supplement contains the first systematic review of the data surrounding the use of injectable risperidone, Reference Fleischhacker9 as well as providing valuable critical updates on diverse LAI-related areas such as pharmacology, attitudes to LAIs, FGA–LAIs compared with oral FGA medications, LAIs and community compulsion, the nursing perspective and a snapshot of English prescribing patterns.

Utilisation rates

Long-acting injection utilisation rates vary greatly internationally, with lower rates seen in France and the USA. Reference Dencker and Axelsson10 In countries such as Australia and the UK, the higher rates of use are currently approximately 30% of patients with schizophrenia, Reference Barnes, Shingleton-Smith and Paton6 and only a minority of these individuals are subjected to compulsory treatment. This is confirmed by recent data from Scotland, which revealed that of 2323 patients with schizophrenia, 34% were prescribed an LAI, of whom 15% were detained (further information available on request). However, even in these countries, the rate of use declined considerably following the introduction of the oral second-generation antipsychotics (SGA–orals) in the 1990s. Reference Johnson and Wright11Reference Callaly and Trauer15 Subsequently the knowledge base and skills associated with prescribing FGA–LAIs arguably declined, leaving a younger generation of psychiatrists at risk of diminished experience. In turn this may further add to the decline in LAI utilisation. For SGA–LAIs there are other restraints, and perhaps the most common of these is their high purchase cost. The cost differential between FGA–LAIs and SGA–LAIs is large. Financial cost does remain an important concern and in certain areas, use has been restricted by those holding the medication budget. Even if others consider depot utilisation rates in the UK to be at a reasonable level already, it remains true that evidence of regional variation exists.

According to systematic reviews approximately 40–60% of patients with schizophrenia are known to be partially or totally non-adherent to oral antipsychotic medication. Reference Cramer and Rosenheck16Reference Zygmunt, Olfson, Boyer and Mechanic18 Long-acting injections are indicated where medication adherence is a cause for concern. Thus it is argued by some that it might seem reasonable to consider such injections for approximately half of patients with schizophrenia, and Valenstein et al reported that 61% of patients with schizophrenia had difficulties with adherence at some point over a 4-year period. Reference Valenstein, Ganoczy, McCarthy, Myra Kim, Lee and Blow19 However, the dearth of long-term studies comparing outcomes between oral medication and long-acting injections remains an important cautionary note. The studies that do exist are old, of poor methodological quality, short in follow-up duration and usually underpowered. When an LAI is prescribed, attendance in clinic for a regular injection every 1–6 weeks guarantees delivery of medication and assists in the process of regular review. Reference Wistedt20 Covert non-adherence can be overcome as it is immediately obvious to the clinician when the patient has not been given an injection. Reference Levine, Schooler and Cassano21 This early detection of non-adherence also facilitates the opportunity for early contact with the patient, and discussion about the reasons for non-adherence, including unintentional forgetfulness and disorganisation.

Intentional and overt non-adherence with LAIs does, of course, also occur. However, findings of two systematic reviews on LAIs suggested a non-adherence rate of only 24% (range 0–54%). Reference Young, Zonana and Shepler22,Reference Young, Spitz, Hillbrand and Danieri23 Three subsequent studies investigated patients who remained on LAIs for 12 months. Heyscue et al reported an overall ‘adherence proportion’ of 0.96 (the adherence proportion is the ratio of kept appointments to scheduled appointments for LAI administration). Reference Heyscue, Levin and Merrick24 In a later study 26% were reported to have poor adherence, based on the duration of missed injections. Reference Tattan and Creed25 Most recently, Shi et al calculated the mean medication possession ratio (cumulative number of days covered by depot divided by 365 days) to be 91% for patients receiving FGA–LAIs. Reference Shi, Ascher-Svanum, Zhu, Faries, Montgomery and Marder26 This implies that adherence rates are better with LAIs than with oral formulations. However, it seems that LAIs have lower than expected prescribing rates, i.e. 28–36% of patients with schizophrenia, Reference Paton, Barnes, Cavanagh and Taylor27Reference Barnes, Paton, Hancock, Cavanagh, Taylor and Lelliott29 but the prescribing practice of an individual psychiatrist is subject to many factors (see Appendix). Reference Patel and David2,Reference Waddell and Taylor30,Reference Gray, Spilling, Burgess and Newey31

Allowing for the differences between FGA–LAIs and SGA–LAIs, some believe that LAIs as a group are underused. Reference Kane, Aguglia, Altamura, Ayuso Gutierrez, Brunello and Fleischhacker32Reference Glazer34 It should be noted that LAIs are unable to prevent relapse completely; even in clinical trials there is an irreducible 20–25% of patients who relapse despite receiving an LAI. Reference Adams, Fenton, Quraishi and David35 If patients discontinue LAI treatment their risk of relapse increases, but if a patient relapses despite regular injections then non-adherence can be safely excluded as the cause. Reference Barnes and Curson14 Although the evidence base for examining the potential gains of LAI use over oral preparations remains inadequate,294,Reference Fleischhacker9,Reference Adams, Fenton, Quraishi and David35 clinicians can use this as a legitimate reason for not increasing LAI usage. Furthermore, the relative merits of prescribing an SGA–LAI over an FGA–LAI are unknown. Perhaps surprisingly, no prospective head-to-head double-blind randomised controlled study has been conducted to date, although recent evidence and debate have suggested that the efficacy of SGA–orals is not superior to that of FGA–orals. Reference Lieberman, Stroup, McEvoy, Swartz, Rosenheck and Perkins36Reference Kahn, Fleischhacker, Boter, Davidson, Vergouwe and Keet38 That said, a good study of LAIs would be of long duration since the most salient outcomes go beyond efficacy in terms of symptom control and extend to relapse prevention, rehospitalisation and mortality. Until such studies are done, clinicians are likely to choose one LAI over another according to preference of side-effect profile for each individual patient, and perhaps cost.

Long-acting injections and polypharmacy

A recurring theme in this supplement is antipsychotic polypharmacy and the use of LAIs. Reference Johnson3,Reference Barnes, Shingleton-Smith and Paton6,Reference Taylor39 We note that antipsychotic polypharmacy is more common in those prescribed an LAI. Reference Barnes, Shingleton-Smith and Paton6 Is such polypharmacy always a ‘bad thing’, and are there circumstances in which it makes good pharmacological sense to use this approach? Reference Correll, Rummel-Kluge, Corves, Kane and Leucht40 Certainly it is a part of our prescribing heritage, Reference Johnson and Wright11 and the practice is common in many countries.

There may be a perception that the side-effects of LAIs are worse than those of oral preparations of the same drug, contrary to the available evidence, Reference Patel and David2,Reference Haddad, Taylor and Niaz4,Reference Patel, Nikolaou and David33,Reference Taylor39 and this belief may be fuelled by the use of polypharmacy. It may also be that when clozapine fails, owing to lack of efficacy or non-adherence, prescribers look to LAIs to provide adherence and then add another oral antipsychotic (i.e. polypharmacy) to attempt to compensate for single-agent lack of efficacy in known treatment resistance.

Stigma and LAIs: what's in a name?

It has been noted that LAIs may have an ‘image problem’. Reference Patel, Nikolaou and David33 This is especially true for FGA–LAIs. Many proponents of SGA–LAIs have attempted to dodge this by rejecting the term ‘depot’, which was perceived to be stigmatising, in favour of ‘long-acting injection’, although some have argued that a new word had to be used anyway because of the different nature of the drug, implying that it was not a ‘true’ depot. In 2002 the belief that second-generation antipsychotics were superior in all ways – including efficacy, adherence and side-effect profile – was common. Reference Jones, Barnes, Davies, Dunn, Lloyd and Hayhurst37,Reference Voruganti, Cortese, Oyewumi, Cernovsky and Awad41,Reference Davis, Chen and Glick42 Those with a vested interest seemed to work hard to deter prescribers from associating SGA–LAIs with their older FGA–LAI counterparts. Choosing a collective term for this group of medications was difficult. Underpinning this whole argument was the debate about how to overcome the potential for discrimination associated with the word ‘depot’, as it was felt that it was perceived by some (but not all) clinicians as stigmatising. After debate, the collective term ‘long-acting injection’ was chosen to cover both first- and second-generation antipsychotics in this formulation, with the subcategories of FGA–LAI and SGA–LAI. This was partly an attempt to move away from stigmatising stereotypes, and also to promote therapeutic optimism for a population for whom hope can be all too scarce.

Conclusion

The problems facing psychiatrists, patients and their carers 40 years ago, when FGA–LAIs were first introduced, Reference Johnson3 remain observable today. Non-adherence to antipsychotic medication is still a key concern, particularly with regard to relapse prevention. Approximately 50% of patients with schizophrenia are partially or totally non-adherent to their antipsychotic regimen but only 30% or less are prescribed an LAI, although of course injections only have a chance to work if they are accepted. Heres et al inform us that, as psychiatrists, we grossly underestimate the numbers of our own patients who are non-adherent, Reference Heres, Hamann, Kissling and Leucht43 and anxieties about LAIs are in some cases based on suboptimal knowledge. Reference Waddell and Taylor30,Reference Patel, Nikolaou and David33 Thus, psychiatrists may not even think to consider discussing with their patients the option of prescribing an LAI. This situation is complicated by the fact that LAIs are unable to prevent relapse completely, Reference Adams, Fenton, Quraishi and David35 and there is also a virtual absence of high-quality head-to-head comparisons of oral and LAI antipsychotic formulations. Naturalistic studies of risperidone LAI report attrition rates higher than those seen in randomised controlled trials and the reasons for this are not fully understood. These are gaps in knowledge and behaviour that should concern us.

Long-acting injection prescribing will evolve in the future, and associated clinical guidelines will require regular updates, Reference Kane and Garcia-Ribera44 as seen in the recent update of the National Institute for Health and Clinical Excellence (NICE) guidelines for schizophrenia. 45 This guidance states that LAIs should be considered for those who prefer such treatment, and when avoidance of covert non-adherence is a clinical priority. It is conceivable that LAI prescribing will increase in the coming years as more SGA–LAIs will be made available, and the increasing use of compulsory community treatment orders may contribute to this. Reference Lambert, Singh and Patel46 The evidence base supporting (or otherwise) LAIs needs to be substantially updated and improved so that the ‘gaps’ will diminish and more appropriate use of LAIs can occur. Perhaps the most critical issue to be addressed is the need for definitive evidence from randomised controlled trials as to whether or not SGA–LAIs are superior, in terms of clinical outcomes, to their respective oral formulations. This needs to be considered particularly in those who have a history of prior oral non-adherence. Surprisingly, these studies have still not been conducted for risperidone LAI, and we urge industry and other funding bodies to consider this a true priority. Other new studies might address FGA–LAIs v. SGA–LAIs (efficacy and tolerability), the use of ‘real world’ outcomes such as mortality and relapse rates, and the nature of the clinician–patient interaction when LAIs are used.

We also hope that the use of long-acting injections occurs within the context of a therapeutic relationship, where both clinician and patient are working in collaboration, and the option of an LAI is discussed openly and not merely as a last resort. Thus, informed patient choice for LAIs may truly occur and the adverse image and associated stigma of this formulation can be reduced.

Appendix

Long-acting injections v. oral formulations

Advantages of long-acting injections over oral formulations

  1. (a) Easier early detection of relapse, improved relapse prevention and reduced rehospitalisation rates

  2. (b) More predictable and stable serum concentrations for first-generation antipsychotic long-acting injections (FGA–LAIs)

  3. (c) Enhanced consistency between the drug prescription and drug delivery of the active drug

  4. (d) Less steady-state interpatient blood level variability for a given dose

  5. (e) Reduced risk of accidental or deliberate self-poisoning

  6. (f) Facilitated differentiation between lack of efficacy and poor adherence

Advantages of oral formulations over LAIs

  1. (a) Possibility of rapid discontinuation enables rapid response to serious adverse side-effects

  2. (b) Patient has enhanced sense of autonomy

  3. (c) Patient perceived as being at less risk of stigma and discrimination

  4. (d) Less frequent attendance at clinic is possible (as can self-administer medication)

Clinicians' fears and expectations

  1. (a) Psychiatrists' beliefs that LAIs are associated with worse side-effects than the equivalent drug in its oral preparation, despite lack of evidence to suggest this

  2. (b) Concerns regarding patients' acceptance of LAIs, yet patients already on this formulation often prefer it

  3. (c) Concerns regarding stigmatising effect of prescribing an LAI, although overcoming stigma and discrimination is not best dealt with by avoidance

  4. (d) Concerns regarding reduced patient autonomy in the context of LAI utilisation, but this could be more to do with the fact that patients are less involved in decision-making at the point that LAIs are prescribed and it is this that needs to be addressed rather than the use of LAIs per se

  5. (e) Concerns regarding nursing staff involvement in administering LAIs and updating training and reducing time pressures on staff so that they can adequately and routinely monitor symptoms and side-effects

  6. (f) Budget holders giving preferential treatment to more fashionable early intervention services and medication rather than maintenance services and medication

  7. (g) Prescriber knowledge and experience about LAIs may be suboptimal, resulting in use of inadequate dose and/or premature discontinuation of treatment with subsequent poor clinical outcomes

(Adapted from Patel & David. Reference Patel and David2 )

Footnotes

Declaration of interest

M.X.P. and A.S.D. have been reimbursed for attendance at scientific conferences and have received consultation fees from Janssen-Cilag and Eli Lilly. They have also received investigator-initiated grants from Janssen-Cilag and Eli Lilly and have previously worked on two clinical drug trials for Janssen-Cilag. M.T. has received hospitality and advisory or speaker fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Janssen-Cilag within the past 5 years.

References

1 Davis, JM, Matalon, L, Watanabe, MD, Blake, L. Depot antipsychotic drugs. Place in therapy. Drugs 1994; 47: 741–73.CrossRefGoogle ScholarPubMed
2 Patel, MX, David, AS. Why aren't depot antipsychotics prescribed more often, and what can be done about it? Advan Psychiatr Treat 2005; 11: 203–13.Google Scholar
3 Johnson, DAW. Historical perspective on antipsychotic long-acting injections. Br J Psychiatry 2009; 195 (suppl 52): s712.Google Scholar
4 Haddad, PM, Taylor, M, Niaz, OS. First-generation antipsychotic long-acting injections v. oral antipsychotics in schizophrenia: systematic review of randomised controlled trial and observational studies. Br J Psychiatry 2009; 195 (suppl 52): s208.Google Scholar
5 Robinson, D, Woerner, MG, Alvir, JMJ, Bilder, R, Goldman, R, Geisler, S, et al. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry 1999; 56: 241–7.Google Scholar
6 Barnes, TRE, Shingleton-Smith, A, Paton, C. Antipsychotic long-acting injections: prescribing practice in the UK. Br J Psychiatry 2009; 195 (suppl 52): s3742.CrossRefGoogle Scholar
7 Miles, CP. Conditions predisposing to suicide: a review. J Nerv Ment Dis 1977; 164: 231–46.Google Scholar
8 Palmer, BA, Pankratz, VS, Bostwick, JM. The lifetime risk of suicide in schizophrenia. Arch Gen Psychiatry 2005; 62: 247–53.Google Scholar
9 Fleischhacker, WW. Second-generation antipsychotic long-acting injections: systematic review. Br J Psychiatry 2009; 195 (suppl 52): s2936.CrossRefGoogle Scholar
10 Dencker, SJ, Axelsson, R. Optimising the use of depot antipsychotics. CNS Drugs 1996; 6: 367–81.CrossRefGoogle Scholar
11 Johnson, DAW, Wright, NF. Drug prescribing for schizophrenic out-patients on depot injections: repeat surveys over 18 years. Br J Psychiatry 1990; 156: 827–34.Google Scholar
12 Shah, AK. Prescribing patterns in a psychiatric follow-up clinic. Psychiatr Bull 1991; 15: 484–5.CrossRefGoogle Scholar
13 Galletly, CA. Antipsychotic drug doses in a schizophrenia inpatient unit. Aust N Z J Psychiatry 1992; 26: 574–6.Google Scholar
14 Barnes, TRE, Curson, DA. Long-acting depot antipsychotics: a risk–benefit assessment. Drug Saf 1994; 10: 464–79.Google Scholar
15 Callaly, T, Trauer, T. Patterns of use of antipsychotic medication in a regional community mental health service. Australas Psychiatry 2000; 8: 220–4.Google Scholar
16 Cramer, JA, Rosenheck, R. Compliance with medication regimens for mental and physical disorders. Psychiatr Serv 1998; 49: 196201.CrossRefGoogle ScholarPubMed
17 Pinikahana, J, Happell, B, Taylor, M, Keks, NA. Exploring the complexity of compliance in schizophrenia. Issues Ment Health Nurs 2002; 23: 5123–8.CrossRefGoogle ScholarPubMed
18 Zygmunt, A, Olfson, M, Boyer, CA, Mechanic, D. Interventions to improve medication adherence in schizophrenia. Am J Psychiatry 2002; 159: 1653–64.Google Scholar
19 Valenstein, M, Ganoczy, D, McCarthy, JF, Myra Kim, H, Lee, TA, Blow, FC. Antipsychotic adherence over time among patients receiving treatment for schizophrenia. A retrospective review. J Clin Psychiatry 2006; 67: 1542–50.Google Scholar
20 Wistedt, B. How does the psychiatric patient feel about depot treatment, compulsion or help? Nord J Psychiatry 1995; 49 (suppl 35): 41–6.Google Scholar
21 Levine, J, Schooler, NR, Cassano, GB. The role of depot neuroleptics in the treatment of schizophrenic patients. Psychol Med 1979; 9: 383–6.Google Scholar
22 Young, JL, Zonana, HV, Shepler, L. Medication noncompliance in schizophrenia: codification and update. Bull Am Acad Psychiatry Law 1986; 14: 105–22.Google Scholar
23 Young, JL, Spitz, RT, Hillbrand, M, Danieri, G. Medication adherence failure in schizophrenia: a forensic review of rates, reasons, treatments and prospects. J Am Acad Psychiatry Law 1999; 27: 426–44.Google Scholar
24 Heyscue, BE, Levin, GM, Merrick, JP. Compliance with depot antipsychotic medication by patients attending outpatient clinics. Psychiatr Serv 1998; 49: 1232–4.CrossRefGoogle ScholarPubMed
25 Tattan, TMG, Creed, FH. Negative symptoms of schizophrenia and compliance with medication. Schizophr Bull 2001; 27: 149–55.Google Scholar
26 Shi, L, Ascher-Svanum, H, Zhu, B, Faries, D, Montgomery, W, Marder, SR. Characteristics and use patterns of patients taking first-generation depot antipsychotics or oral antipsychotics for schizophrenia. Psychiatric Serv 2007; 58: 482–8.Google Scholar
27 Paton, C, Barnes, TRE, Cavanagh, MR, Taylor, D, Lelliott P, the POMH–UK project team. High-dose and combination antipsychotic prescribing in acute adult wards in the UK; the challenges posed by p.r.n. prescribing. Br J Psychiatry 2008; 192: 435–9.Google Scholar
28 Barnes, TRE, Paton, C, Cavanagh, MR, Hancock, E, Taylor, DM. A UK audit of screening for the metabolic side effects of antipsychotics in community patients. Schizophr Bull 2007; 33: 1397–401.Google Scholar
29 Barnes, TRE, Paton, C, Hancock, E, Cavanagh, MR, Taylor, D, Lelliott, P. Screening for the metabolic syndrome in community psychiatric patients prescribed antipsychotics: a quality improvement programme. Acta Psychiatr Scand 2008; 118: 2633.Google Scholar
30 Waddell, L, Taylor, M. Attitudes of patients and mental health staff to antipsychotic long-acting injections: systematic review. Br J Psychiatry 2009; 195 (suppl 52): s4350.CrossRefGoogle Scholar
31 Gray, R, Spilling, R, Burgess, D, Newey, T. Antipsychotic long-acting injections in clinical practice: medication management and patient choice. Br J Psychiatry 2009; 195 (suppl 52): s516.Google Scholar
32 Kane, JM, Aguglia, E, Altamura, AC, Ayuso Gutierrez, JL, Brunello, N, Fleischhacker, WW, et al. Guidelines for depot antipsychotic treatment in schizophrenia. Eur Neuropsychopharmacol 1998; 8: 5566.Google Scholar
33 Patel, MX, Nikolaou, V, David, AS. Psychiatrists' attitudes to maintenance medication for patients with schizophrenia. Psychol Med 2003; 33: 83–9.CrossRefGoogle ScholarPubMed
34 Glazer, WM. The depot paradox. Behav Healthcare 2007; 27: 44–6.Google ScholarPubMed
35 Adams, CE, Fenton, MKP, Quraishi, S, David, AS. Systemic meta-review of depot antipsychotic drugs for people with schizophrenia. Br J Psychiatry 2001; 179: 290–9.CrossRefGoogle Scholar
36 Lieberman, JA, Stroup, S, McEvoy, JP, Swartz, MS, Rosenheck, RA, Perkins, DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353: 1209–23.Google Scholar
37 Jones, PB, Barnes, TR, Davies, L, Dunn, G, Lloyd, H, Hayhurst, KP, et al. Randomized controlled trial of effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia. Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry 2006; 63: 1079–87.Google Scholar
38 Kahn, RS, Fleischhacker, WW, Boter, H, Davidson, M, Vergouwe, Y, Keet, IPW, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 2008; 371: 1085–97.CrossRefGoogle ScholarPubMed
39 Taylor, D. Psychopharmacology and adverse effects of antipsychotic long-acting injections. Br J Psychiatry 2009; 195 (suppl 52): s139.CrossRefGoogle Scholar
40 Correll, CU, Rummel-Kluge, C, Corves, C, Kane, JM, Leucht, S. Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomised controlled trials. Schizophr Bull 2009; 35: 443–57.Google Scholar
41 Voruganti, L, Cortese, L, Oyewumi, L, Cernovsky, Z, Awad, A. Comparative evaluation of conventional and novel antipsychotic drugs with reference to their subjective tolerability, side-effect profile and impact on quality of life. Schizophr Res 2000; 43: 135–45.CrossRefGoogle ScholarPubMed
42 Davis, JM, Chen, N, Glick, ID. A meta-analysis of the efficacy of second-generation antipsychotics. Arch Gen Psychiatry 2003; 60: 553–64.CrossRefGoogle ScholarPubMed
43 Heres, S, Hamann, J, Kissling, W, Leucht, S. Attitudes of psychiatrists toward antipsychotic depot medication. J Clin Psychiatry 2006; 67: 1948–53.CrossRefGoogle ScholarPubMed
44 Kane, JM, Garcia-Ribera, C. Clinical guideline recommendations for antipsychotic long-acting injections. Br J Psychiatry 2009; 195 (suppl 52): s637.Google Scholar
45 National Collaborating Centre for Mental Health. Schizophrenia: Core Interventions in the Treatment and Management of Schizophrenia in Adults in Primary and Secondary Care (Update). Clinical Guideline CG82. NICE, 2009 (http://www.nice.org.uk/nicemedia/pdf/CG82NICEGuideline.pdf).Google Scholar
46 Lambert, TJ, Singh, BS, Patel, MX. Community treatment orders and antipsychotic long-acting injections. Br J Psychiatry 2009; 195 (suppl 52): s5762.CrossRefGoogle Scholar
Submit a response

eLetters

No eLetters have been published for this article.