Long-term antipsychotic use and brain changes in schizophrenia - a systematic review and meta-analysis

Huhtaniska, Sanna; Jääskeläinen, Erika; Hirvonen, Noora; Remes, Jukka; Murray, Graham K.; Veijola, Juha; Isohanni, Matti

doi:10.1002/hup.2574

Cited by 68 publications

(41 citation statements)

References 82 publications

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“…45 These findings suggest that the effects of dysregulation within these brain systems are complicated by competing influences on activity and affective expression. 10,51 It is also possible that subject groups are qualitatively different, in that at least some of the first-episode subjects may represent individuals who will not go on to experience further episodes. While a lower glutamate signal must be interpreted with some caution, this finding is consistent with a relative decrease in network activity.…”

Section: Discussionmentioning

confidence: 99%

“…In addition while subjects were medication free when scanned, they were not necessarily medication naïve; although lithium has been observed to have neuroprotective rather than pathological properties, recent meta-analyses examining possible neurostructural effects of antipsychotic exposure have been mixed. 10,51 It is also possible that subject groups are qualitatively different, in that at least some of the first-episode subjects may represent individuals who will not go on to experience further episodes. However, the known natural history of bipolar I disorder and the relatively greater symptoms in the first episode patients militate against this concern.…”

Section: Discussionmentioning

confidence: 99%

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Neurophysiological effects of multiple mood episodes in bipolar disorder

et al. 2019

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Objectives: Bipolar disorder is marked by progressive symptomatic changes, which have been linked with episode-related structural findings-particularly in the prefrontal cortex. However, few studies have examined neurofunctional and neurochemical effects of disease burden. In this study, we compared first-and multi-episode bipolar individuals. We hypothesized that the latter would demonstrate evidence of neurophysiological differences consistent with a model of progressive functional degradation of these networks. Methods:First-and multi-episode manic bipolar subjects participated in functional magnetic resonance imaging (fMRI) including a continuous performance task with emotional distractors, and in single-voxel ( 1 H) magnetic resonance spectroscopy (MRS). A priori fMRI regions-of-interest (ROI) included structures comprising prefrontal-striatal-amygdala networks; ( 1 H)MRS voxels were placed within bilateral ventrolateral prefrontal (VLPFC) and anterior cingulate cortex (ACC). Both ROI and voxel-based brain activation in response to emotional stimuli, and neurochemical concentrations derived from ( 1 H)MRS were compared across bipolar groups.Results: Multi-episode bipolar subjects showed relatively lower regional activation across prefrontal-striatal-amygdala networks, including bilateral VLPFC, orbitofrontal cortex, ACC, putamen, caudate, and amygdala. Exploratory whole-brain, voxel-based analysis suggested additional areas of lower activation extending into Brodmann area 22, posterior parietal regions, and right thalamus. Glutamate and N-acetylaspartate (NAA) concentrations were also relatively lower in the ACC of multi-episode subjects.Conclusions: Disease burden, exemplified by multiple affective episodes is associated with evidence of widespread decrements in affective network activity. Lower ACC NAA concentration is similarly consistent with a model of progressive functional deficits. These findings support the functional significance of previously observed progressive structural changes throughout these regions. K E Y W O R D Sbipolar disorder, fMRI, mania, MRS, neuroprogression

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neurophysiological effects of multiple mood episodes in bipolar disorder

et al. 2019

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“…According to our previous meta-analysis on long-term antipsychotic effects on brain structures, higher antipsychotic doses associated with decrease in parietal lobe volume and increase in basal ganglia volume (Huhtaniska et al, 2017a). A recent very large cross-sectional study pooling data from over 4000 schizophrenia patients found associations between medication dose and lower cortical thickness in multiple regions, which persisted after controlling for negative symptom severity (van Erp et al 2018).…”

Section: Introductionmentioning

confidence: 99%

“…The current key treatment of psychosis, regardless of its aetiology or the underlying illness, is antipsychotic medication. Suggested harmful effects of high dose long-term antipsychotic treatment on brain structure volumes in psychoses are a debated issue with no consensus (Fusar-Poli et al, 2013;Huhtaniska et al, 2017a). Gray matter reductions have also been detected in populations at high risk for psychosis (Wood et al, 2008) and drug naïve first episode schizophrenia patients (Leung et al, 2011), which most likely reflects the pathological process leading to illness onset.…”

Section: Introductionmentioning

confidence: 99%

Antipsychotic and benzodiazepine use and brain morphology in schizophrenia and affective psychoses – Systematic reviews and birth cohort study

Huhtaniska

Korkala

Heikka

et al. 2018

Psychiatry Research: Neuroimaging

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The aim of this paper was to investigate differences in brain structure volumes between schizophrenia and affective psychoses, and whether cumulative lifetime antipsychotic or benzodiazepine doses relate to brain morphology in these groups. We conducted two systematic reviews on the topic and investigated 44 schizophrenia cases and 19 with affective psychoses from the Northern Finland Birth Cohort 1966. The association between lifetime antipsychotic and benzodiazepine dose and brain MRI scans at the age of 43 was investigated using linear regression. Intracranial volume, sex, illness severity, and antipsychotic/benzodiazepine doses were used as covariates. There were no differences between the groups in brain structure volumes. In schizophrenia, after adjusting for benzodiazepine dose and symptoms, a negative association between lifetime antipsychotic dose and the nucleus accumbens volume remained. In affective psychoses, higher lifetime benzodiazepine dose associated with larger volumes of total gray matter and hippocampal volume after controlling for antipsychotic use and symptoms. It seems that in addition to antipsychotics, the severity of symptoms and benzodiazepine dose are also associated with brain structure volumes. These results suggest, that benzodiazepine effects should also be investigated also independently and not only as a confounder.

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“…Adverse effects attributable to chronic antipsychotic exposure are often cumulative over a period of years. A meta‐analysis found associations between long‐term antipsychotic use and brain volume changes. Antipsychotics may also impact on brain plasticity and cognitive functioning.…”

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confidence: 99%

Under‐utilized opportunities to optimize medication management in long‐term treatment of schizophrenia

et al. 2018

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Long-term antipsychotic use and brain changes in schizophrenia - a systematic review and meta-analysis

Abstract: Antipsychotic medication may associate with brain structure changes. More long-term follow-up studies taking into account illness severity measures are needed to make definitive conclusions.

Cited by 68 publications

References 82 publications

Neurophysiological effects of multiple mood episodes in bipolar disorder

Neurophysiological effects of multiple mood episodes in bipolar disorder

Antipsychotic and benzodiazepine use and brain morphology in schizophrenia and affective psychoses – Systematic reviews and birth cohort study

Under‐utilized opportunities to optimize medication management in long‐term treatment of schizophrenia

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