INTRODUCTION

Schizophrenia is the most difficult mental illness to define and describe (Gelder et al. 2000). The course of illness can be poor and life long treatment is needed. An early observation by Kreaplin (Henry & Smeltzer 2003) noted that 2.5% of pa­tients with schizophrenia recover fully but more recent studies (Kane et al. 1988) have been more optimistic quoting 25% full recovery. The same study also found that 10 -15% of patients with schizophre­nia do not recover fully. For this group of patients, a number of them do not re­spond to standard treatment using single anti-psychotic regime and have been coined treatment resistant. Patients who are resistant to treatment have only been shown to respond to clozapine. Cloza­pine however is not without problems, among them agranulocytosis can occurs, which is a fatal complication that may lead to death if not detected and treated early. Keeping this fact in mind, is there a role for polypharmacy?

This case will be used to highlight the rare instances when polypharmacy may be useful prior to the commencement of clozapine for the treatment of schizo­phrenia.

CASE REPORT

A 19 years old college student of Chi­nese descend presented to our center with a week history of aggression and irritability. She was also noted to be talk­ative and there was a history suggestive of depressive illness whereby she was keeping to herself, crying at times and had poor concentration a year before. She however had strong persecutory delusions of being victimized by the pub­lic and kept saying that she was publicly discriminated against. She also claimed to be a special being and able to com­municate with her boy friend telepa­thically whom she blamed to be the rea­son for this. Mentally, she was hostile, but her mood was happy. However her affect was inappropriate, she had flighty ideas and pressure of speech. Her in­sight was poor. She was initially treated for bipolar affective disorder with quetia­pine 400mg twice daily and a mood sta­bilizer, and was discharged 15 days later. She presented the next day with relapse of symptoms when she had sud­denly hit her father in the car and almost caused a motor vehicle accident. During this admission her medication was in­creased and she was discharged 9 days later. She came for one follow up visit but was again admitted two weeks later with relapsing symptoms. Her case was dis­cussed in the postgraduate conference and a revised diagnosis of schizophrenia was made. On this admission, her psy­chotic symptoms were more prominent with persecutory delusions of discrimina­tion, thought broadcasting, neologism, inappropriate affect and intermittent hos­tility. Her mood symptoms had all but disappeared. She received electrocon­vulsive therapy during this admission and aripiprazole at 10mg daily was started. Quetiapine was planned to be tapered off slowly. She was discharged 14 days later with this combination. Dur­ing her admis­sions her biochemical in­vestigations were normal, these included full blood test, renal and liver function test and fasting glucose levels.

She was followed up in the clinic and was compliant to both medication and follow up. The quetipaine was reduced gradually and her aripiprazole was in­creased to 15mg once daily. She re­sponded well to this new regimen until she was on aripiprazole 15mg once daily and quetiapine 200mg at night. A re­duction of quetiapine would bring back the delusions and any increase would make her to become too sedated.

She has since been maintained on this dose and has responded very well. She plans to continue her studies for which she had stopped for eight months. Her family is also very happy with her progress.

DISCUSSION

For the pharmacological treatment of schizophrenia, monotherapy has always been encouraged and advocated in most guidelines(Weiden & Casey 1999, APA 2004). However, polypharmacy has been recognized by some and usually sug­gested as the last resort(Faries et al. 2005). Among reasons why monotherapy is preferred are to allow psychiatrist to accurately evaluate patient’s response to the new treatment(Weiden & Casey 1999) to allow adequate trial of each medication, to reduce the complexity of the medication regimen, to reduce side effects and also to assess and manage future symptom exacerba­tions(Miller & Craig 2002).

The literature has very little evidence supporting the use of polypharmacy with atypical antipsychotics and is divided on its long-term use this way(Stahl & Grady 2004, Picker et al 2008). Although poly­pharmacy has been used for a variety of reasons with the favorite being to bolster medication effectiveness in treating pa­tients with refractory psychotic symp­toms, mood symptoms or behavioral problems, the risk of combining two atypical antipsychotic appears to out­weigh the benefits (Stahl & Grady 2004). Among these risk is a potentially higher mortality and an increase in metabolic problems(Faries et al. 2005, Stahl 2004).

For our patient, polypharmacy appears to work well for her. It has given her an option to recover fully. It has also saved her the option of treatment with clozapine which was impending in view of her poor response to quetiapine and aripiprazole at high doses individually. Although clo­zapine has been proven for difficult cases like our patient, the side effects and regular blood monitoring may be cumbersome given other options in treatment. The use of aripiprazole which is claimed to be weight neutral and less sedating (Lieberman 2004) is better suited for a young and active individual and will hopefully encourage compliance. Although the combination of aripiprazole and quetiapine has not been studied in detail, her low dose of quetiapine at night may be useful for sleep as it is more se­dating but may not be sufficient to cause weight gain as a side effect.

Another explanation which may explain her response to this combination could well be that she had improved on the dose of aripiprazole 15mg which she has been taking for more than 3 months. The relapse of symptoms when quetiapine was titrated down and when ariprazole was increased could well be due to aka­thesia, or inner restlessness, which is a known side effect in the initial stages. It can be very discomforting to the patient and may lead her to have a persecutory type of delusion.

Whichever the explanation, in the end it is all about the patient and her recovery that matters most.