1 APRIL 2022 ausdoc . com . au

Figure 8 . Treatment algorithm for schizophrenia .

Add benzodiazepine

• Aggression / agitation , eg , diazepam

• Anxiety , eg , lorazepam

• Sleep disturbance , eg , temazepam

Physical and psychiatric assessment

Allow an antipsychotic drug-free assessment phase

Psychiatric emergency

Initiate antipsychotic treatment

Start low and go slow

Differential diagnoses

If depressive or manic symptoms are evident , consider other disorders that include psychosis :

• Bipolar I disorder with psychotic features

• Schizoaffective disorder

• Major depressive disorder with psychotic features

PAGE 38 medications can be changed by tapering one and introducing and increasing the dose of the other . Take care that the overall dose equivalence is not changed significantly as a marked reduction in equivalent dose risks relapse . Also anticipate the reduction of old adverse effects ( for example , a loss of sedation and consequent insomnia ) and prepare for any new adverse effects . ²⁵ Exercise special care when changing to or from clozapine as a rapid reduction in clozapine dose risks a severe relapse .

CLOZAPINE An increasing number of GPs are being asked to take over the day-to-day management of patients on clozapine . ²⁶ Clozapine is the most effective of the antipsychotic medications for the treatment of schizophrenia and it is indicated for those who have not responded to at least two other adequate trials of antipsychotics ( adequate dose for an adequate duration ) or have significant difficulties with movement disorders or aggression . ²⁷ However , its use is limited because of the number and potential severity of adverse effects .

Clozapine initiation is usually done by the specialist team caring for the patient . The drug requires a slow upward titration and weekly FBC monitoring for agranulocytosis for the first 18 weeks , and thereafter monthly . When the patient ’ s mental state has stabilised and they have started monthly monitoring , care is increasingly transferred back to GPs . GPs require registration and specific training with the local clozapine monitoring service . Continued six monthly review by a specialist psychiatrist is required . Clozapine can only be dispensed by specific registered pharmacies .

Clozapine requires close medical follow-up , not just because of the risk of agranulocytosis ( 2-3 %), but also for a plethora of other serious adverse effects such as myocarditis ( 1 %) and cardiomyopathy ( rare ),

Table 3 . RANZCP clinical practice guidelines for schizophrenia Agent

Anticholinergic effects

Second generation antipsychotic agents

Dyslipidaemia

Extrapyramidal side effects

Sedation

Weight gain

Amisulpride — ? + — +++ — + + ++ Aripiprazole + — + — — + — — ^a — Asenapine ^b + ++ + ++ + + + + + Clozapine +++ ^c +++ — +++ =/— +++ ^d +++ +++ + Lurasidone — — + ^e +/— ++ ^e — — ^f +/— — Olanzapine ++ +++ +/— +++ + + ++ +++ + Paliperidone + + + + +++ +++ ^d + ++ + Quetiapine + ++ + +++ + ++ ++ ++ ++ Risperidone + ++ + ++ +++ ++ ^d + ^d ++ + Sertindole — — — — + + ^g — + +++ Ziprasidone + — + + ++ + + + ++ First generation antipsychotic agents Chlorpromazine +++ +++ ++ +++ +++ +++ ^h +++ +++ ++ Flupenthixol ++ ? ++ ++ +++ + + ++ + Fluphenazine + ? +++ ++ +++ + + +++ + Haloperidol + + +++ ⁱ ++ +++ + + ^h ++ ++ Pericyazine +++ ? + + ^j +++ ++ +++ ++ ? Trifluoperazine + ? +++ + +++ ++ + ++ ? Zuclopenthixol ++ ^c ? ++ + ^j +++ + +++ ++ ?

QTc prolongation

Sources : Table adapted with permission from Therapeutic Guidelines — Psychotropic version 7 ( Psychotropic Writing Group , 2013 ); data on QTc prolongation from The Maudsley prescribing Guidelines in Psychiatry ( Taylor et al ., 2015 ); data on lurasidone from various sources ( Australian Government Therapeutic Goods Administration , 2014 ; Citrome , 2013 ; Leucht et al ., 2013 ; Peuskens et al ., 2014 ). ?: Little or no information reported ; –: Negligible or absent ; +: Infrequent ; ++: Moderately frequent ; +++: Frequent . The information in this table is based on a combination of reported adverse effect data and expert opinion ; it is intended only as a guide and should be interpreted in the context of the person ’ s particular situation ( e . g . concurrent drugs , drug history , physical health , the considerable inter-individual variation in elimination half-lives ) and doses . a

Weight loss reported . b

Data on the frequencies of asenapine adverse effects are limited . c

Hypersalivation reported . d

Frequency may be higher at the start of therapy or with rapid dose increase . e

Appears to be dose-related . f

Somnolence is a common observed dose-related adverse effect . g

Frequency may be higher with rapid dose increase , but data are conflicting . h

More frequent with rapid dose increase . i

Lower incidence with LAI formulation . j

Reported to occur but no definitive data published as to the incidence . Source : Galletly C et al . Australian and New Zealand Journal of Psychiatry . 2016 ; 50 ( 5 ): 410-472 ¹⁶