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Prescribing guidelines for first episode psychosis

First line
NICE recommends oral antipsychotics are prescribed first line for newly diagnosed
schizophrenia1.The first line drug prescribed is dependent on patient and carer
choice following adequate explanation.
Based on up to date evidence, first line recommended antipsychotic options are:
o Amisulpride
o Aripiprazole
o Quetiapine
o Risperidone
o Sulpiride
All drugs listed in this guideline are in alphabetical order
Second Generation Antipsychotics (SGA) appear to have greater efficacy for
negative symptoms than First Generation Antipsychotics (FGA), although the
CATIE and CUtLASS studies showed that no difference in psychosocial outcomes
were evident2,3,4,5,6. Sulpiride is the only FGA included as a first line choice due to
recent evidence2,7.
All antipsychotics (except clozapine) are assumed of equal efficacy for the
treatment of positive symptoms. We await further evidence from independent
effectiveness trials.
Clinician input to process should focus on matching profile of drug to patient profile.
Drugs with notable potential for major adverse effects are:
1. Initial sedation: Amisulpride, FGAs, Olanzapine, Quetiapine. Risperidone,
Sulpiride.
2. Metabolic adverse effects: SGAs but notably Clozapine and Olanzapine.
Aripiprazole may not cause these effects8.
3. Movement disorders: FGAs.
4. Hyperprolactinaemia: Amisulpride, FGAs, Risperidone, Sulpiride.
Long-term effects of raised prolactin include sexual and reproductive impairment
and reduced bone density (young females likely more vulnerable) 9. This is a
notable area for ongoing review.
Dose: It should be noted that doses of amisulpride > 300mg/day are licensed for
twice daily administration. Sulpiride and immediate-release quetiapine are also
licensed for twice daily administration. However, all of the first line options appear
to be effective when administered once daily. See below for off licence prescribing
guidance.

Switch if:
1. Non-response at 4 weeks10. If partial response consider increasing dose (if
tolerated) and longer trial10.
2. Intolerable or potentially harmful side effects.
3. Patient request / non-adherence related to nature of drug.
Second line
Additional oral alternatives 2nd line to those above are olanzapine (efficacy could
be favourable above others after first episode use11,12), or a low dose FGA such as
haloperidol1,2,3.
Olanzapine is a second line option because of the relative increased risks of
metabolic effects13.
Long acting injectable medication (risperidone in first instance) should be
considered, particularly if there is evidence of poor concordance14,15. When
considering the use of risperidone long acting injection refer to Trust guidelines.
Third line
If intolerant or non-adherent, choose other first or second line antipsychotic.
Do not delay offering clozapine if treatment resistant after the second step. This
should not be held in reserve at this stage.
Baseline investigations and monitoring to be conducted as per Trust and NICE
guidelines1.
Additional information for treatment of people under 18 with antipsychotic
medication
Not all antipsychotics are licensed for use in those under 18 years of age.
Several FGAs are licensed for use in children to treat schizophrenia. For example,
haloperidol is licensed from age 12 years and sulpiride from age 14 years.
Amisulpride and aripiprazole are licensed for the treatment of schizophrenia in
patients aged 15 years and over.
Clozapine is licensed for the treatment of schizophrenia in patients unresponsive
to, or intolerant of, conventional antipsychotic drugs from age 16 years.
Olanzapine, quetiapine and risperidone are licensed for the treatment of
schizophrenia in patients aged 18 years and over.
Ideally, medication should be prescribed within the terms of the marketing
authorisation. However, it is recognised that this in not always practical especially
as second generation antipsychotics may have a more favourable side effect
profile in this patient age group16. When prescribing outside of product licence this

should be discussed and a joint decision made with the client and the discussion
must be documented. A Sussex Partnership Trust leaflet and medication consent
forms are available to aid this discussion.
The BNF for children gives further guidance on licensed and unlicensed
prescribing.
Cost implications
Antipsychotic costs for 28 days treatment (taken from Drug Tariff May 2009)17
Based on commonly used average doses for first episode psychosis (Brighton
locality);
Amisulpride
Aripiprazole
Haloperidol
Olanzapine
Quetiapine
Quetiapine XL
Risperidone
Sulpiride

400mg/day
10mg/day
1.5mg/day
10mg/day
600mg/day
600mg/day
4mg/day
800mg/day

53.44
97.67
1.62
79.45
158.67
158.67
27.74
19.53

All prices are based on standard tablet formulation (orodispersible and liquid
preparations may cost considerably more).
Clozapine is the only antipsychotic with an evidence base for use in treatment
resistant schizophrenia, hence at this stage cost implications are obsolete.
However, clozapine therapy is no longer expensive compared to other SGAs.
These guidelines will be reviewed three monthly in light of new data.
Richard Whale
Louise Noble
Jacqui Freeman
Gail Kavanagh
Victoria Lukats
Date agreed: May 2009
Date reviewed: September 2009
Review date: December 2009

References
1. CG82 Schizophrenia (update): NICE guideline 2009. www.nice.org.uk.
2. Jones PB, Barnes TR, Davies L, 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.

3. Keefe RS, Bilder RM, Davis SM, Harvey PD, Palmer BW, Gold JM, Meltzer
HY, Green MF, Capuano G, Stroup TS, McEvoy JP, Swartz MS, Rosenheck
RA, Perkins DO, Davis CE, Hsiao JK, Lieberman JA, for the CATIE
Investigators and the Neurocognitive Working Group. Neurocognitive effects
of antipsychotic medications in patients with chronic schizophrenia in the
CATIE trial. Arch Gen Psychiatry 2007; 64: 63347.
4. Erhart SM, Marder SR, Carpenter WT. Treatment of schizophrenia negative
symptoms: future prospects. Schizophr Bull. 2006; 32:234-7.
5. Danion JM, Rein W, Fleurot O. Improvement of schizophrenic patients with
primary negative symptoms treated with amisulpride. Amisulpride study
group. Am J Psychiatry. 1999; 156: 610-16.
6. Olie JP, Spina E, Murray S et al. Ziprasidone and amisulpride effectively
treat negative symptoms of schizophrenia: results of a 12-week, doubleblind study. Int Clin Psychopharmacol. 2006; 21: 143-51.
7. Soares BG, Fenton F, Chue P. Sulpiride for schizophrenia. Cochrane
Library, issue 4, 2008. http://www.thecochranelibary.com.
8. American Psychiatric Association:Practice Guideline for the treatment of
patients with schizophrenia, 2nd ed, Am J Psychiatry 2004;161 (suppl).
9. Meaney AM, OKeane V. Bone mineral density changes over a year in
young females with Schizophrenia. Schizophrenia Research. 2007; 93: 136143.
10. Agid O, Kapur S, Arenovich T, et al. Delayed-Onset Hypothesis of
Antipsychotic Action. Arch Gen Psychiatry 2003; 60: 1228-1235.
11. Stroup TS, Lieberman JA, McEvoy JP, Swartz MS, Davis SM, Rosenheck
RA, Perkins DO, Keefe RS, Davis CE, Severe J, Hsiao JK. Effectiveness of
Olanzapine, Quetiapine, Risperidone, and Ziprasidone in Patients With
Chronic Schizophrenia Following Discontinuation of a Previous Atypical
Antipsychotic. for the CATIE Investigators Am J Psychiatry. 2006; 163: 611
622.
12. Leucht S, Komossa K, Rummel-Kluge C, Corves C, Hunger H, Schmid F,
Asenjo Lobos C, Schwarz S, Davis JM. A Meta-Analysis of Head-to-Head
Comparisons of Second-Generation Antipsychotics in the Treatment of
Schizophrenia. Am J Psychiatry 2009; 166: 152 - 163.
13. Proudlove C. Metabolic adverse effects with atypical antipsychotic agents.
NeLM In-Focus Review. Published 09/05/2008.
14. Tiihonen J, Walhbeck K, Lnnqvist J, Klaukka T, Ioannidis JPA, Volavka J,
Haukka J. Effectiveness of antipsychotic treatments in a nationwide cohort
of patients in community care after first hospitalisation due to schizophrenia
and schizoaffective disorder: observational follow-up study. BMJ 2006; 333:
224.
15. Hogarty GE, Schooler NR, Ulrich R, Mussare F, Ferro P, Herron E.
Fluphenazine and Social Therapy in the Aftercare of Schizophrenic Patients:
Relapse Analyses of a Two-Year Controlled Study of Fluphenazine
Decanoate and Fluphenazine Hydrochloride. Arch Gen Psychiatry 1979; 36:
1283 - 1294.
16. Kumra S, Oberstar JV, Sikich L et al. Efficacy and Tolerability of SecondGeneration Antipsychotics in Children and Adolescents with Schizophrenia.
Schizophr Bull. 2008; 34: 60-71.
17. The Drug Tariff. May 2009. Available online
www.nhsbsa.nhs.uk/prescriptions.