Module 3 – Case Study 2: Initiating Depot Antipsychotics
Joyce's Pharmaceutical Care Plan
Joyce is 22 years old and has had frequent admissions to mental health units in the region.
She was diagnosed with schizophrenia at the age of 19, in the second year of her Bachelor of
Arts degree at University.
History at presentation: Joyce is a young female diagnosed with schizophrenia in early
adulthood. She lives alone; thus has had minimal supervision with oral medications leading to
medication non-compliance, for which she has required frequent admissions to hospital for reestablishing her medication management. Joyce’s previous medication was olanzapine 10mg
daily, and more recently risperidone 3mg. She showed a good response to both treatments.
Her presenting symptoms on admission include: anxiety and poor sleep. She was reported
again to be non-compliant with her medications prior to this admission. Immediately after admission, she was restarted on risperidone at a dose of 4mg daily, with a good initial response. Joyce’s DSM-IV multi-axial diagnosis is summarized below:
Axis I – Relapse of schizophrenia due to medication non-compliance
Axis II – No reported personality disorders or mental retardation
Axis III – No concomitant medical condition
Axis IV – Failed to complete a distance learning IT course
Axis V – Global Assessment of Functioning (GAF) score is unavailable.
Management: The most important management goal for Joyce is to minimize the risk of relapse due to non-compliance with her medication regimen. Her noncompliance history is putting her at increased risk for worsening her prognosis (Joyce has had multiple admissions over the last year that has resulted in her failing to complete a distance learning IT course she had enrolled in).
Achieving a better compliance will likely result in symptom control for extended periods of time, reducing the likelihood of admissions for re-establishing medication management. This intervention alone will likely improve her quality of life and functionality. Alternatives for achieving medication compliance (such as blister-packs, close-control dispensing, reminder phone calls, psychoeducation) have been attempted with Joyce, but most (if not all) have failed. Thus, she should be initiated on a depot antipsychotic as another alternative to achieve medication compliance. It is regarded that depot antipsychotics lead to better adherence as they need to be administered less regularly than oral medications (ex: once a month, fortnightly, etc.). However, their use will also need to be agreed upon and have patient acceptance, possibly through suitable education, and more especially in someone like Joyce.
As Joyce has been already initiated on oral risperidone, ideally she should be switched to the
same medication on a depot formulation. Depot risperidone (available as microspheres) can be prescribed through the Special Authority for subsidy under the following Pharmac criteria:
As explained above, Joyce is a suitable candidate for depot risperidone. Alternativeley, she could also be started on a typical depot antipsychotic which pharmacologically resembles the dopamine blocking effects of risperidone. Haloperidol would also be a suitable typical depot antipsychotic agent.
Initiation of depot antipsychotic medication: Some reports utilize formulas and conversion
factors to calculate the dose of a particular depot antipsychotic after oral treatment (this information is adequately reviewed in the CD-ROM on depot antipsychotics, which also contains a useful dosing convertor which is easy to use). However, it is actually more important to use judgement in a particular situation or consider individual patient characteristics at the time of initiating depot treatment, rather than routinely utilizing a particular formula for switching from oral to depot antipsychotics. Given the fact that the depot drugs can overcome problems such as inadequate absorption or rapidly metabolizing the oral drugs, the dosage required can be different from that from employing a simple conversion formula.
The strategy for initiating a depot drug will vary depending upon factors such as prior drug dosage and clinical state. Some recommend initial loading dose, some a more gradual titration. The need to supplement with oral medication should be considered particularly in the first 4 to 6 weeks. Abrupt discontinuation of oral medication should be avoided whenever possible. Depot medication dosage should be increased over a 2-3 month period. Careful surveillance during this transition is extremely important.
As discussed above, the most recommended treatment choice for Joyce is to switch her from oral to depot risperidone. It is recommended that patients such as Joyce who are receiving a dosage of up to 4mg oral risperidone daily should begin at 25mg Risperdal Consta every two weeks, with a minimum of 3 injections (6 weeks) before steady state is achieved and a review of the dose should occur then. Recent literature reports a steady state is achieved after 3 x 2/52 injections, with therapeutic plasma levels after week 3. At this point Joyce should be reviewed as to whether a further dose increase to 37.5mg would be required. It is important to continue with the oral risperidone up to this 3-week period, at which point it is suggested that under monitored clinical supervision, the oral dose can be safely discontinued - there is no need to titrate down. For further information, you can view the Medsafe datasheet available from:
http://www.medsafe.govt.nz/Profs/Datasheet/r/RisperdalConstainj.htm
If the alternative option of starting Joyce on a typical atypical agent is preferred, the following strategy would be recommended: Joyce’s current oral dose of risperidone is 4mg/day. It has been suggested that a 2mg dose is approximately equivalent to 5mg of haloperidol. Therefore, Joyce is taking an approximate equivalent haloperidol dose of 10 mg/day. The recommended conversion formula provided for converting from oral to depot haloperidol is:
Haloperidol oral dose x 10-20 times = haloperidol decanoate dose every 4 weeks
Using this conversion table the starting dose for haloperidol would be 100mg every four weeks. However, she is currently taking oral medication, therefore for this alternative Joyce’s depot treatment should probably begin with haloperidol decanoate 50mg. Haloperidol decanoate is usually administered once a month, its pharmacokinetic profile indicates that peaks at 7 days, shows an elimination half-life of 3 weeks, and the time for steady state is 3 months. It is crucial to keep her on the oral risperidone for the next 2-3 weeks before starting to taper down the risperidone dose, and keep her at lower doses for about 3 weeks of depot haloperidol. The depot dosage should be increased as required to achieve the recommended dose over a 2-3 month period. It is important to consider the use of “prn” benztropine or procyclidine for the management of extrapyramidal symptoms (EPS) at the time when the depot antipsychotic peaks, in this case, at about 2-3 weeks after the initial administration of depot haloperidol.
Monitoring Plan: Upon initiation of the depot antipsychotic patients need minimal supervision. However, Joyce should be followed up after two weeks of depot initiation, interviewed and monitored for changes in her initial presenting symptoms, as well as monitoring for EPS, and other potential side effects. The most commonly reported side effects with Risperdal Consta® (with an incidence of 5% at a dose of 25 mg) are: sedation, akathisia, parkinsonism, dyspepsia, constipation, dry mouth, and weight increase of +/- 9% baseline body weight). Advice accordingly for management strategies, including supportive psycho-education around diet and exercise, and encouraging fluid intake, and suggest sugar free gum or sugar free boiled sweets for the anticholinergic effects of the depot risperidone. The use of “prn” anticholinergic medication may also prove beneficial. If this is the case, it is important to monitor for anticholinergic side effects, as they may be bothersome. Other monitoring parameters that may be useful include:
- Baseline prolactin levels (although Joyce has been on oral risperidone for some time, these ‘baselines’ may be elevated. If she is asymptomatic, the level could serve as baseline).
- Liver function tests (major metabolism pathway), renal function (elimination), blood pressure (orthostatic hypotension).
- Baseline fasting glucose and weight.
- Joyce should be asked to speak with the treating team before becoming pregnant, as there is limited current research into pregnancy while on depot risperidone.
- Alcohol use (may cause excessive sedation).
Monitoring for medication efficacy is as important as monitoring for side effects. Looking for a reduction in positive and negative symptoms, as well as increased functionality, is recommended. Asking Joyce and her family to report on the degree to which the side effects are affecting her life, with a view to discussing benefit of medication vs. risk of side effects.