Structural and functional neuroimaging findings associated with the use of clozapine in schizophrenia: a systematic review

Garcia, Giovana; Chagas, Marcos Hortes Nisihara; Silva, Carlos H; Machado‐de‐Sousa, João Paulo; Crippa, José Alexandre de Souza; Hallak, Jaime Eduardo Cecílio

doi:10.1590/1516-4446-2014-1387

Cited by 19 publications

(14 citation statements)

References 48 publications

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“…Despite evidence that clozapine induces distinctive structural changes in grey matter [58], one study included treatment-resistant patients on clozapine while the other did baseline imaging before their first dose of clozapine, suggesting that this pattern should not immediately be dismissed as secondary to clozapine treatment. This pattern corroborates previous studies (not included as they only look at response to a single antipsychotic trial) which have found that smaller grey matter volume is associated with poorer response to haloperidol [59] and a prospective study in first-episode patients finding reduced occipital grey matter predicted lack of response [60].…”

Section: Discussionmentioning

confidence: 99%

Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review

et al. 2017

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BackgroundSchizophrenia is a highly heterogeneous disorder, and around a third of patients are treatment-resistant. The only evidence-based treatment for these patients is clozapine, an atypical antipsychotic with relatively weak dopamine antagonism. It is plausible that varying degrees of response to antipsychotics reflect categorically distinct illness subtypes, which would have significant implications for research and clinical practice. If these subtypes could be distinguished at illness onset, this could represent a first step towards personalised medicine in psychiatry. This systematic review investigates whether current evidence supports conceptualising treatment-resistant and treatment-responsive schizophrenoa as categorically distinct subtypes.MethodA systematic literature search was conducted, using PubMed, EMBASE, PsycInfo, CINAHL and OpenGrey databases, to identify all studies which compared treatment-resistant schizophrenia (defined as either a lack of response to two antipsychotic trials or clozapine prescription) to treatment-responsive schizophrenia (defined as known response to non-clozapine antipsychotics).ResultsNineteen studies of moderate quality met inclusion criteria. The most robust findings indicate that treatment-resistant patients show glutamatergic abnormalities, a lack of dopaminergic abnormalities, and significant decreases in grey matter compared to treatment-responsive patients. Treatment-resistant patients were also reported to have higher familial loading; however, no individual gene-association study reported their findings surviving correction for multiple comparisons.ConclusionsTentative evidence supports conceptualising treatment-resistant schizophrenia as a categorically different illness subtype to treatment-responsive schizophrenia. However, research is limited and confirmation will require replication and rigorously controlled studies with large sample sizes and prospective study designs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-016-1177-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review

et al. 2017

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“…Moreover, effects of medication, namely antipsychotic treatment, performed in all but one patient, cannot be ruled out. However, at least in patients with schizophrenia, conflicting results of either decreased or increased brain perfusion in the frontal cortex due to treatment with antipsychotics have been reported ( 38 , 39 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of Deep Brain Stimulation on Regional Cerebral Blood Flow in Patients with Medically Refractory Tourette Syndrome

et al. 2016

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In this study, alterations in brain perfusion have been investigated in patients with Tourette syndrome (TS) compared with control subjects. In addition, we investigated the effects of deep brain stimulation (DBS) in both globus pallidus internus (GPi) and centromedian-parafascicular/ventralis oralis internus nuclei of the thalamus (CM/Voi) and sham (SHAM) stimulation on cerebral blood flow. In a prospective controlled, randomized, double-blind setting, five severely affected adult patients with TS with predominant motor or vocal tics (mean total tic score on the Yale Global Tic Severity Scale: 39) underwent serial brain perfusion single photon emission computed tomography with 99mTc-ECD. Results were compared with data from six age-matched control subjects. All patients were investigated at four different time points: once before DBS implantation (preOP) and three times postoperatively. Postoperative scans were performed in a randomized order, each after 3 months of either GPi, CM/Voi, or SHAM stimulation. At each investigation, patients were injected at rest while awake, but scanned during anesthesia. This procedure ensured that neither anesthesia nor movement artifacts influenced our results. Control subjects were investigated only once at baseline (without DBS or anesthesia). At baseline, cerebral blood flow was significantly reduced in patients with TS (preOP) compared with controls in the central region, frontal, and parietal lobe, specifically in Brodmann areas 1, 4–9, 30, 31, and 40. Significantly increased perfusion was found in the cerebellum. When comparing SHAM stimulation to preOP condition, we found significantly decreased perfusion in basal ganglia and thalamus, but increased perfusion in different parts of the frontal cortex. Compared with SHAM condition both GPi and thalamic stimulation resulted in a significant decrease in cerebral blood flow in basal ganglia and cerebellum, while perfusion in the frontal cortex was significantly increased. Our results provide substantial evidence that, in TS, brain perfusion is altered in the frontal cortex and the cerebellum and that these changes can be reversed by both GPi and CM/Voi DBS.

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“…Klozapinin beyindeki etkileri manyetik rezonans görüntüleme (MRG), tek foton emisyon sintigrafisi (SPECT), pozitron emisyon tomografisi (PET) ve 1 H-MRS çalışmalarıyla incelenmiştir. Yapısal görüntüleme çalışmalarında klozapinin, tipik antipsikotiklerle meydana gelen bazal ganglia hacmindeki artışı geri döndürebildiği; sağlıklı kontrollere göre klozapin kullananlarda toplam gri cevher beyin hacminin fazla, beyaz cevher hacminin düşük olduğu gösterilmiştir (Garcia ve ark. 2015).…”

Section: Introductionunclassified

Effect of Clozapine on Proton Magnetic Resonance Spectroscopy Findings in Hippocampus

Eroğlu¹,

Ertuğrul²,

Oğuz³

et al. 2020

Turkish Journal of Psychiatry

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Bu çalışmada şizofreni hastalarında klozapin tedavisinin hipokampus üzerindeki etkilerinin proton manyetik rezonans spektroskopi (1 H-MRS) ile değerlendirilmesi amaçlanmış; metabolit düzeylerindeki değişimle psikopatoloji ve bilişsel işlevlerdeki değişim arasındaki ilişki incelenmiştir. Yöntem: Şizofreni hastaları (n=16) 12 haftalık klozapin tedavisi öncesi ve sonrası 1 H-MRS, Pozitif ve Negatif Sendrom Ölçeği (PANSS), Klinik Global İzlenim Ölçeği (KGİ) ve nörobilişsel test bataryasıyla; sağlıklı kontroller (n:8) bir kez nörobilişsel test bataryası ve 1 H-MRS'le değerlendirilmiştir. 1 H-MRS'de sağ ve sol hipokampus multivoksel ve sol hipokampus tek voksel ölçümlerinde NAA/Cr, Cho/Cr, MI/Cr oranları hesaplanmıştır. Bulgular: İzlem sonrasında tedavinin başlangıcına göre PANSS ve KGİ puanlarında azalma, Rey İşitsel-Sözel Öğrenme Testi anlık hatırlama ve toplam öğrenme, Sözel Akıcılık Kategori Testi, Wechsler Bellek Ölçeği gecikmiş bellek test puanlarında artma gözlenmiştir. Hipokampus multivoksel ve tek voksel ölçümlerinde NAA/Cr, Cho/ Cr, MI/Cr düzeylerinde klozapin öncesinde hasta grubuyla sağlıklı kontroller arasında; hastalarda 12 haftalık klozapin tedavisi öncesi ve sonrası arasında fark olmadığı saptanmıştır. 1 H-MRS'yle ölçülen metabolit düzeylerindeki değişimle psikopatoloji puanları ve bilişsel test puanlarındaki değişim arasında ilişki saptanmamıştır. Sonuç: Klozapinin hipokampustaki 1 H-MRS bulguları üzerine etkilerini inceleyen ilk uzunlamasına çalışmadır. Klozapin tedavisiyle 1 H-MRS bulgularında anlamlı değişiklik saptanmamıştır. Bu konuda nihai bir sonuca varmak için klozapinin daha geniş örneklem ve daha uzun izlem süresi içeren çalışmalarla incelenmesi gereklidir.

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Structural and functional neuroimaging findings associated with the use of clozapine in schizophrenia: a systematic review

Cited by 19 publications

References 48 publications

Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review

Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review

Effect of Deep Brain Stimulation on Regional Cerebral Blood Flow in Patients with Medically Refractory Tourette Syndrome

Effect of Clozapine on Proton Magnetic Resonance Spectroscopy Findings in Hippocampus

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