Aripiprazole Add-On Treatment in a Patient with Schizoaffective Disorder: Neurocognitive Outcomes

Aripiprazole, a dopamine receptor partial agonist, has been suggested to enhance cognitive functioning in psychosis. Whereas some studies reveal a potential advantage of aripiprazole over other new generation antipsychotics in this regard [6] [8], others do not consistently confirm these findings [5] [10]. We report here on a patient with schizoaffective disorder treated with olanzapine who experienced neurocognitive deterioration despite clinical remission, and in whom an add-on therapy with aripiprazole was started in order to potentially improve cognitive functioning.

Mr. A., a 43-year-old man, was diagnosed with schizoaffective disorder (ICD-10) in Paris in 1997 where he had taken up residence a few months before for occupational reasons. His family history was free of mental illness, and he had no personal history of seizures or head trauma. Introduction of olanzapine to 20 mg/day led to clinical remission, and the patient returned to Austria. In 1998, he stopped medication and was first admitted to our hospital, experiencing disorganized thought, delusions, and manic mood. Treatment with olanzapine was resumed, and the patient remitted again. Within the last ten years, Mr. A. regularly attended our specialized outpatient clinic. Three additional inpatient treatments were required because of relapse.

With regard to pharmacological therapy Mr. A. was predominantly treated with olanzapine up to 30 mg/day. Temporarily, on the patient's request, treatment with olanzapine was replaced by quetiapine (600 mg/day) and risperidone (4 mg/day), respectively. However, as he achieved only partial symptom remission during these treatments and add-on treatment with lithium (900 mg/day) and valproate (1 500 mg/day), respectively, did not change his medical condition, monotherapy with olanzapine was resumed in April 2005 and led to symptomatic and functional remission.

In July 2008, Mr. A. complained about a decrease in neurocognitive functioning concentrating predominantly on a decline of retentiveness, which finally caused a loss of employment. As he was still fully remitted from a symptomatic point of view (PANSS [4] total score: 36), an add-on treatment with aripiprazole 15 mg/day was started while continuing olanzapine 30 mg/day in order to potentially improve his cognitive functioning. At this time the patient had been in remission for years from a symptomatic point of view. Therefore, no clinical reason was evident to switch to monotherapy with aripiprazole as we did not want to risk symptomatic deterioration.

The following neurocognitive tests were given three times within 15 weeks: Verbal learning and memory were assessed using the “Münchner Gedächtnistest” (MGT) [3], a German equivalent of the “California Verbal Learning Test” [2], which was used in an ABA design to avoid practice effects. Variables of interest were (a) the total number of words recalled in the five learning trials, (b) short free and (c) short cued recall, (d) long free and (e) long cued recall, and (f) recognition. Working memory was tested by using the subtest “digit span” (DS) out of the German version of the “Wechsler Adult Intelligence Scale” (WAIS-III) [1], whereas processing speed was assessed by using the subtest “digit symbol coding” (DSC) out of the same test. Levels of sustained and selective attention were investigated by using a brief K-A version (360 letters) of the “Continuous Performance Test” (CPT) [7], speed of information processing was assessed using the “Trail Making Test” (TMT-A/B) [9].

Cognitive outcomes are presented in [Table 1] . At baseline, the learning curve in MGT did already not significantly rise, and a further decline in verbal learning and memory was apparent in nearly all examined fields over time. Furthermore, at week 15 the patient showed a marked deterioration in TMT-B performance. Next to a slight enhancement in DSC performance from below average to average at week 15 performances of DS, CPT, and TMT-A consistently remained on average.

Table 1 Scores on measures of neurocognition. Measurea Baseline Week 6 Week 15 a Abbrevations: MGT=Münchner Gedächtnistest, WAIS-III=Wechsler Adult Intelligence Scale, CPT=Continuous Performance Test, TMT-A/B=Trail Making Test A/B MGT memory (min – max; N) 6–10 3–12 4–9 short free recall (N) 7 4 5 short cued recall (N) 8 7 10 long free recall (N) 8 9 5 long cued recall (N) 10 9 7 recognition (N) 14 13 12 WAIS-III digit span (N) 9 9 9 digit symbol coding (N) 6 6 7 CPT omissions (N) 5 6 4 commissions (N) 67 66 68 false alarms (N) 3 4 7 TMT A (s) 24.80 24.0 26.6 B (s) 59 73 >121

Add-on treatment with aripiprazole was stopped by week 15 because of the lack of a neurocognitive benefit. Furthermore, even though no symptomatic change could be established, Mr. A. had developed hypersalivation as a side effect which remitted after cessation of aripiprazole.

Clearly, the development of antipsychotic medications has had a profound effect on the treatment of schizophrenia, but the cognitive deficits associated with this disorder have been insufficiently addressed. It is therefore critical to continue the search for novel approaches such as combining new generation antipsychotics with different modes of action to achieve meaningful gains in this regard. Whereas the open label study reported by Kern et al. [5] suggests that the neurocognitive effects of monotherapy with aripiprazole are comparable with those of olanzapine, the presented single case does not support a further amelioration of cognitive functioning when combining these compounds. However, it has to be emphasized that it would be premature to draw far-ranging clinical conclusions from the findings of this case report due to its very restricted internal and external validity. Therefore, the topic clearly warrants further study in randomized controlled trials.

References

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