Ten Years of Improving Acute Stroke Management in a Metropolitan Area: A Population-Based Quantification of Quality Indicators.

BACKGROUND AND PURPOSE: Rapid access to acute stroke treatment improves clinical outcomes in patients with ischemic stroke. We aimed to shorten the time to admission and to acute stroke treatment for patients with acute stroke in the Hamburg metropolitan area by collaborative multilevel measures involving all hospitals with stroke units, the Emergency Medical Services (EMS), and health-care authorities. METHODS: In 2007, an area-wide stroke care quality project was initiated. The project included mandatory admission of all stroke patients in Hamburg exclusively to hospitals with stroke units, harmonized acute treatment algorithms among all hospitals, repeated training of the EMS staff, a multimedia educational campaign, and a mandatory stroke care quality monitoring system based on structured data assessment and quality indicators for procedural measures. We analyzed data of all patients with acute stroke who received inhospital treatment in the city of Hamburg during the evaluation period from the quality assurance database data and evaluated trends of key quality indicators over time. RESULTS: From 2007 to 2016, a total of 83,395 patients with acute stroke were registered. During this period, the proportion of patients admitted within ≤3 h from symptom onset increased over time from 27.8% in 2007 to 35.2% in 2016 (p < 0.001). The proportion of patients who received rapid thrombolysis (within ≤30 min after admission) increased from 7.7 to 54.1% (p < 0.001). CONCLUSIONS: Collaborative stroke care quality projects are suitable and effective to improve acute stroke care.

Dabigatran or Aspirin After Embolic Stroke of Undetermined Source in Patients With Patent Foramen Ovale: Results From RE-SPECT ESUS.

BACKGROUND AND PURPOSE: Patent foramen ovale (PFO) may increase the risk of embolic stroke of undetermined source (ESUS). Guidelines suggest anticoagulation may be more effective than antiplatelets in preventing stroke in patients with ESUS and PFO when interventional closure is not performed. METHODS: Patients with ESUS randomized to dabigatran (150/110 mg BID) or aspirin (100 mg QD) from the RE-SPECT ESUS study (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) were included. The rate of recurrent stroke (primary end point) and ischemic stroke was reported for patients with and without baseline PFO. A meta-analysis comparing the effects of anticoagulant and antiplatelet therapy on ischemic stroke in patients with PFO was updated to include RE-SPECT ESUS. RESULTS: PFO was present in 680 of 5388 (12.6%) patients with documented PFO status. The risk of recurrent stroke with dabigatran versus aspirin was similar in patients with and without PFO (P for interaction, 0.8290). In patients with PFO, the meta-analysis found no statistically significant difference between anticoagulant and antiplatelet therapy (odds ratio, 0.70 [95% CI, 0.43-1.14]) for ischemic stroke. CONCLUSIONS: There is insufficient evidence to recommend anticoagulation over antiplatelet therapy for patients with ESUS and a PFO. More data are needed to guide antithrombotic therapy in this population. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239120.

Platelet function testing in transient ischaemic attack and ischaemic stroke: A comprehensive systematic review of the literature.

The majority of patients with ischaemic cerebrovascular disease (CVD) are not protected from further vascular events with antiplatelet therapy. Measurement of inhibition of platelet function ex vivo on antiplatelet therapy, using laboratory tests that correlate with the clinical effectiveness of these agents, would potentially enable physicians to tailor antiplatelet therapy to suit individuals. A systematic review of the literature was performed to collate all available data on ex vivo platelet function/reactivity in CVD patients, especially those treated with aspirin, dipyridamole or clopidogrel. Particular emphasis was paid to information from commonly available whole blood platelet function analysers (PFA-100®, VerifyNow® and Multiplate®). Data on pharmacogenetic mechanisms potentially influencing high on-treatment platelet reactivity (HTPR) on antiplatelet therapy in CVD were reviewed. Two-hundred forty-nine potentially relevant articles were identified; 93 manuscripts met criteria for inclusion. The prevalence of ex vivo HTPR in CVD varies between 3-62% with aspirin monotherapy, 8-61% with clopidogrel monotherapy and 56-59% when dipyridamole is added to aspirin in the early, subacute or late phases after TIA/stroke onset. The prevalence of HTPR on aspirin was higher on the PFA-100 than on the VerifyNow in one study (p < 0.001). Furthermore, the prevalence of HTPR on aspirin was lower when one used 'novel longitudinal' rather than 'cross-sectional, case-control' definitions of HTPR on the PFA early after TIA or stroke (p = 0.003; 1 study). Studies assessing the influence of genetic polymorphisms on HTPR in CVD patients are limited, and need validation in large multicentre studies. Available data illustrate that an important proportion of CVD patients have ex vivo HTPR on their prescribed antiplatelet regimen, and that the prevalence varies depending on the definition and assay used. Large, adequately-sized, prospective multicentre collaborative studies are urgently needed to determine whether comprehensive assessment of HTPR at high and low shear stress with a range of user-friendly whole blood platelet function testing platforms, in conjunction with pharmacogenetic data, improves our ability to predict the risk of recurrent vascular events in CVD patients, and thus enhance secondary prevention following TIA or ischaemic stroke.

Stroke risk after posterior circulation stroke/transient ischemic attack and its relationship to site of vertebrobasilar stenosis: pooled data analysis from prospective studies.

BACKGROUND AND PURPOSE: Recent prospective studies have shown vertebrobasilar (VB) stenosis predicts stroke risk in posterior circulation stroke and transient ischemic attack. It is unclear whether this association is independent of other risk factors, and whether intracranial or extracranial stenosis confers different risks. METHODS: A pooled individual patient analysis of data from 2 prospective studies was performed in 359 patients presenting with VB transient ischemic attack or stroke. Contrast-enhanced magnetic resonance angiography, or computed tomography angiogram, and clinical follow-up were available in 323 patients. Risk of stroke was calculated from any VB transient ischemic attack/stroke in the month before the presenting episode (first event) and from the presenting event. A systematic review of similar prospective studies was performed. RESULTS: Ninety-day risk of stroke from the first event was 24.6% in patients with VB stenosis versus 7.2% in those without (odds ratio, 4.2; 95% confidence interval, 2.1-8.6; P<0.0001). Risk was higher (33%) with intracranial (odds ratio, 6.5; 2.8-15.0; P<0.0001) than extracranial stenosis (16.2%; odds ratio, 2.5; 0.9-6.8; P=0.06). Risk from the presenting event was 9.6% in patients with stenosis versus 2.8% in those without (odds ratio, 3.7; 1.2-11.0; P=0.012), and again the risk was higher with intracranial stenosis. Cox regression showed the risk associated with VB stenosis was independent of other cardiovascular risk factors. The systematic review identified only 1 other report, which included only 6 patients. CONCLUSIONS: Symptomatic VB stenosis, particularly intracranial stenosis, is a strong independent predictor of stroke recurrence. The high early risk of stroke provides a strong rationale for randomized trials to determine whether stenting can reduce risk.

Continuous stroke unit electrocardiographic monitoring versus 24-hour Holter electrocardiography for detection of paroxysmal atrial fibrillation after stroke.

BACKGROUND AND PURPOSE: Cardioembolism in paroxysmal atrial fibrillation (pxAF) is a frequent cause of ischemic stroke. Sensitive detection of pxAF after stroke is crucial for adequate secondary stroke prevention; the optimal diagnostic modality to detect pxAF on stroke units is unknown. We compared 24-hour Holter electrocardiography (ECG) with continuous stroke unit ECG monitoring (CEM) for pxAF detection. METHODS: Patients with acute ischemic stroke or transient ischemic attack were prospectively enrolled. After a 12-channel ECG on admission, all patients received 24-hour Holter ECG and CEM. Additionally, ECG monitoring data underwent automated analysis using dedicated software to identify pxAF. Patients with a history of atrial fibrillation or with atrial fibrillation on the admission ECG were excluded. RESULTS: Four hundred ninety-six patients (median age, 69 years; 61.5% male) fulfilled all inclusion criteria (ischemic stroke: 80.4%; transient ischemic attack: 19.6%). Median stroke unit stay lasted 88.8 hours (interquartile range, 65.0-122.0). ECG data for automated CEM analysis were available for a median time of 64.0 hours (43.0-89.8). Paroxysmal AF was documented in 41 of 496 patients (8.3%). Of these, Holter detected pxAF in 34.1%; CEM in 65.9%; and automated CEM in 92.7%. CEM and automated CEM detected significantly more patients with pxAF than Holter (P<0.001), and automated CEM detected more patients than CEM (P<0.001). CONCLUSIONS: Automated analysis of CEM improves pxAF detection in patients with stroke on stroke units compared with 24-hour Holter ECG. The comparative usefulness of prolonged or repetitive Holter ECG recordings requires further evaluation.

Lower rates of intervention for symptomatic carotid stenosis in women than in men reflect differences in disease incidence: a population-based study.

BACKGROUND AND PURPOSE: Although there is little sex difference in the age-specific incidence of transient ischemic attack (TIA) and stroke, substantially more men than women undergo endarterectomy/stenting for symptomatic carotid stenosis. Sexism in referral for investigation or intervention has been proposed as an explanation; however, a lower incidence of carotid disease in women or reluctance to undergo intervention might also be responsible. METHODS: We determined the sex-specific incidence of symptomatic carotid stenosis and subsequent endarterectomy/stenting from 2002 to 2009 in consecutive patients with TIA or nondisabling ischemic stroke in the Oxford Vascular Study. We studied equivalent data from routine clinical practices in the wider Oxfordshire population. RESULTS: There was no sex difference in age-specific referral rates for carotid imaging in the Oxford Vascular Study (n=616; age-adjusted relative rate [RR] for males vs females=1.08; 95% CI, 0.79 to 1.46; P=0.64). However, rates of 50% to 99% symptomatic carotid stenosis were higher in men (RR=1.89; 95% CI, 1.31 to 2.71; P=0.0005). The same was seen in imaged patients (n=575) in the wider Oxfordshire population (RR=1.82; 95% CI, 1.31 to 2.53; P=0.003) and in pooled data (RR=1.87; 95% CI, 1.32 to 2.64; P=0.0003). Rates of symptomatic carotid occlusion were also higher in men in both populations (RR=3.19; 95% CI, 1.95 to 5.23; P<0.0001). Consequently, although men were more likely to undergo carotid intervention (RR=1.98; 95% CI, 1.43 to 2.75; P<0.0001), the proportion of patients with 50% to 99% symptomatic carotid stenosis who received intervention was similar for men and women (odds ratio=1.13; 95% CI, 0.57 to 2.25; P=0.72). CONCLUSIONS: Lower rates of intervention for 50% to 99% symptomatic carotid stenosis in women can be explained by sex differences in population-based incidence. We found no evidence of any investigation or intervention bias.

Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: a prospective, population-based study.

BACKGROUND AND PURPOSE: The annual risk of ischemic stroke distal to > or =50% asymptomatic carotid stenoses was approximately 2% to 3% in early cohort studies and subsequent randomized trials of endarterectomy. This risk might have fallen in recent years owing to improvements in medical treatment, but there are no published prognostic data from studies initiated within the last 10 years. METHODS: In a population-based study of all patients with transient ischemic attack (TIA) or stroke in the Oxford Vascular Study, we studied the risk of TIA and stroke in patients with > or =50% contralateral asymptomatic carotid stenoses recruited consecutively from 2002 to 2009 and given intensive contemporary medical treatment. RESULTS: Of 1153 consecutively imaged patients presenting with stroke or TIA, 101 (8.8%) had > or =50% asymptomatic carotid stenoses (mean age, 75 years; 39% women; 40% age > or =80 years). During 301 patient-years of follow-up (mean, 3 years), there were 6 ischemic events in the territory of an asymptomatic stenosis, 1 minor stroke (initially 50% to 69% stenosis), and 5 TIAs (2 initially 50% to 69% stenosis; 3 to 70% to 99% stenosis), 3 of which led to subsequent endarterectomy. The average annual event rates on medical treatment were 0.34% (95% CI, 0.01 to 1.87) for any ipsilateral ischemic stroke, 0% (95% CI, 0.00 to 0.99) for disabling ipsilateral stroke, and 1.78% (95% CI, 0.58 to 4.16) for ipsilateral TIA. CONCLUSIONS: In the first study of the prognosis of > or =50% asymptomatic carotid stenosis to be initiated in the last 10 years, the risk of stroke on intensive contemporary medical treatment was low. Larger studies are required to determine whether this apparent improvement in prognosis is generalizable.

Platelet function/reactivity testing and prediction of risk of recurrent vascular events and outcomes after TIA or ischaemic stroke: systematic review and meta-analysis.

BACKGROUND: The prevalence of ex vivo 'high on-treatment platelet reactivity (HTPR)' and its relationship with recurrent vascular events/outcomes in patients with ischaemic cerebrovascular disease (CVD) is unclear. METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA statement. MEDLINE, EMBASE and Cochrane Library were searched for completed manuscripts until May 2019 on TIA/ischaemic stroke patients, ≥ 18 years, treated with commonly-prescribed antiplatelet therapy, who had platelet function/reactivity testing and prospective follow-up data on recurrent stroke/TIA, myocardial infarction, vascular death or other cerebrovascular outcomes. Data were pooled using random-effects meta-analysis. Primary outcome was the composite risk of recurrent stroke/TIA, myocardial infarction or vascular death. Secondary outcomes were recurrent stroke/TIA, severe stroke (NIHSS > 16) or disability/impairment (modified Rankin scale ≥ 3) during follow-up. RESULTS: Antiplatelet-HTPR prevalence was 3-65% with aspirin, 8-56% with clopidogrel and 1.8-35% with aspirin-clopidogrel therapy. Twenty studies (4989 patients) were included in our meta-analysis. There was a higher risk of the composite primary outcome (OR 2.93, 95% CI 1.90-4.51) and recurrent ischaemic stroke/TIA (OR 2.43, 95% CI 1.51-3.91) in patients with vs. those without 'antiplatelet-HTPR' on any antiplatelet regimen. These risks were also more than twofold higher in patients with vs. those without 'aspirin-HTPR' and 'dual antiplatelet-HTPR', respectively. Clopidogrel-HTPR status did not significantly predict outcomes, but the number of eligible studies was small. The risk of severe stroke was higher in those with vs. without antiplatelet-HTPR (OR 2.65, 95% CI 1.00-7.01). DISCUSSION: Antiplatelet-HTPR may predict risks of recurrent vascular events/outcomes in CVD patients. Given the heterogeneity between studies, further prospective, multi-centre studies are warranted.

Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison.

BACKGROUND: The risk of recurrent stroke is up to 10% in the week after a transient ischaemic attack (TIA) or minor stroke. Modelling studies suggest that urgent use of existing preventive treatments could reduce the risk by 80-90%, but in the absence of evidence many health-care systems make little provision. Our aim was to determine the effect of more rapid treatment after TIA and minor stroke in patients who are not admitted direct to hospital. METHODS: We did a prospective before (phase 1: April 1, 2002, to Sept 30, 2004) versus after (phase 2: Oct 1, 2004, to March 31, 2007) study of the effect on process of care and outcome of more urgent assessment and immediate treatment in clinic, rather than subsequent initiation in primary care, in all patients with TIA or minor stroke not admitted direct to hospital. The study was nested within a rigorous population-based incidence study of all TIA and stroke (Oxford Vascular Study; OXVASC), such that case ascertainment, investigation, and follow-up were complete and identical in both periods. The primary outcome was the risk of stroke within 90 days of first seeking medical attention, with independent blinded (to study period) audit of all events. FINDINGS: Of the 1278 patients in OXVASC who presented with TIA or stroke (634 in phase 1 and 644 in phase 2), 607 were referred or presented direct to hospital, 620 were referred for outpatient assessment, and 51 were not referred to secondary care. 95% (n=591) of all outpatient referrals were to the study clinic. Baseline characteristics and delays in seeking medical attention were similar in both periods, but median delay to assessment in the study clinic fell from 3 (IQR 2-5) days in phase 1 to less than 1 (0-3) day in phase 2 (p<0.0001), and median delay to first prescription of treatment fell from 20 (8-53) days to 1 (0-3) day (p<0.0001). The 90-day risk of recurrent stroke in the patients referred to the study clinic was 10.3% (32/310 patients) in phase 1 and 2.1% (6/281 patients) in phase 2 (adjusted hazard ratio 0.20, 95% CI 0.08-0.49; p=0.0001); there was no significant change in risk in patients treated elsewhere. The reduction in risk was independent of age and sex, and early treatment did not increase the risk of intracerebral haemorrhage or other bleeding. INTERPRETATION: Early initiation of existing treatments after TIA or minor stroke was associated with an 80% reduction in the risk of early recurrent stroke. Further follow-up is required to determine long-term outcome, but these results have immediate implications for service provision and public education about TIA and minor stroke.

Inflammatory response after acute ischemic stroke.

BACKGROUND AND PURPOSE: This study aimed to characterize the time course of inflammatory parameters after acute ischemic stroke. METHODS: We serially determined high sensitivity C-reactive protein (CRP), fibrinogen, and leukocyte counts at 10 time points between days 1 and 90 after ischemic stroke and in control subjects. RESULTS: CRP did not significantly change, whereas fibrinogen increased after stroke. At all time points, CRP and fibrinogen were higher than in healthy control subjects, but not risk factor control subjects. The leukocyte count declined after stroke and was significantly elevated as compared to both control groups only on day 1 but not later. NIHSS levels were positively correlated with CRP and fibrinogen at all time points. Larger infarcts were associated with a higher CRP and leukocyte counts on day 90. Treatment with aspirin was associated with lower values for all three inflammatory parameters in the subacute phase after ischemia. CONCLUSIONS: The course after stroke was different between the parameters of inflammation. Only the leukocytes followed the paradigm of an acute phase response.

Use of a telestroke service for evaluation of non-stroke neurological cases.

Telemedicine is a growing field in many medical specialties. Within clinical neurosciences one of its largest applications is in acute stroke care. However, little is known about its value and effect in general neurology, despite stroke. In a retrospective survey of 1500 teleconsultations over a time period of 12 months from October 2008 to September 2009, from a large telestroke network in Germany, we evaluated 352 cases with a non-stroke diagnosis. Duration and methods of teleconsultation as well as neurological consultations at bedside and discharge diagnosis were analyzed and compared to stroke cases. Discharge diagnosis was not identical to teleconsultation diagnosis in 48.9% of all non-stroke cases compared to 12.5% of all stroke cases. Duration of teleconsultation was 26.5 min in non-stroke cases compared to 14.3 min for stroke cases. In non-stroke cases other parts of the neurological examination were added to the pure administration of a stroke scale. There were no significant differences between non-stroke cases with correct and incorrect consultation diagnoses concerning in-hospital mortality (4.6 vs. 5.0%) and length of hospital stay (8.3 vs. 7.6 days). We conclude that diagnostic accuracy and protocol routine is not as exact in non-stroke cases compared to acute stroke cases. Other neurologic conditions may need different algorithms for a telemedicine service. Thus experience from a telestroke service cannot be transferred to other neurologic conditions on a routine basis.

Course of platelet activation markers after ischemic stroke.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the time course of platelet activation after ischemic stroke and to investigate whether platelet activation and inflammation are correlated with each other. METHODS: We serially determined expression of p-selectin (CD62p) and lysosome-associated membrane protein (CD63) by platelets using flow cytometry at 10 time points between days 1 and 90 in patients after ischemic stroke (n=50), in healthy subjects (n=30), and in risk factor control subjects (n=20). Furthermore, we correlated leukocyte count, C-reactive protein, and fibrinogen levels with platelet activation markers. RESULTS: CD62p and CD63 expression was higher on day 1 after stroke than in both control groups (P<0.005 for both). CD62p expression rapidly declined, whereas CD63 expression remained significantly elevated until day 90. Stroke severity and different medication for secondary stroke prevention did not influence CD62p or CD63 expression. Platelet activation markers and inflammatory parameters were not correlated with each other at any time point after stroke. CONCLUSIONS: The initial increase in both CD62p and CD63 expression by platelets is followed by a differential regulation of both parameters after stroke. The rapid decrease in CD62p expression may be caused by shedding from the cell surface. Its persistent elevation makes CD63 a good candidate for studies on predictors for stroke recurrence. Our findings suggest that the expression of CD62p and CD63 by platelets is regulated independently from inflammatory indexes.

Peripheral pulse measurement after ischemic stroke: A feasibility study.

OBJECTIVE: To investigate feasibility and diagnostic accuracy of measurement of the peripheral pulse (MPP) at the radial artery as a simple, noninvasive screening tool for paroxysmal atrial fibrillation (pAF) in patients after acute ischemic stroke. METHODS: Two hundred fifty-six patients with acute ischemic stroke and the patients' relatives at a tertiary stroke center were prospectively included. Participants were instructed for characteristics of atrial fibrillation (AF) in MPP using standardized educational material. Measurements of participants as well as a health care professional were then compared with simultaneous blinded ECG to evaluate diagnostic accuracy parameters. RESULTS: MPP by the health care professional or patients' relatives had a diagnostic sensitivity of 96.5% and 76.5%, respectively, with 94.0% and 92.9% specificity for the detection of AF. Self-measurements were reliably performed by 89.1% of competent patients with a diagnostic sensitivity of 54.1% and 96.2% specificity. False-positive results were limited to 6 cases (2.7%) with a positive predictive value of 76.9% and a negative predictive value of 90.0%. CONCLUSION: With a low rate of false-positive results, MPP offers an easy, ubiquitously available, noninvasive, first-step screening tool to guide ECG diagnostics for pAF after ischemic stroke. The data warrant a prospective trial evaluating the efficacy of MPP-guided ECG diagnostics in secondary prevention after stroke, which is now underway. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that MPP by patients or relatives accurately distinguishes AF from normal heart rhythm as compared with continuous ECG.

Feasibility of certified quality management in a comprehensive stroke care network using telemedicine: STENO project.

BACKGROUND: Stroke care networks with and without telemedicine have been established in several countries over the last decade to provide specialized stroke expertise to patients in rural areas. Acute consultation is a first step in the management of stroke, but not the only one. Methods of standardization of care and treatment are much needed. So far, quality management systems have only been used for single stroke units. To the best of our knowledge, we are the first stroke network worldwide to aim for certification of a network-wide quality management system. METHODS: The Stroke Network Using Telemedicine in Northern Bavaria (STENO), currently with 20 associated medical institutions, is one of the world's largest stroke networks, caring for over 5000 stroke patients each year. In 2010, we initiated the implementation of a network-wide 'total' quality management system according to ISO standard 9001:2008 in cooperation with the German Stroke Society and a third-party certification organization (LGA InterCert). RESULTS: Certification according to ISO 9001:2008 was awarded in March 2011 and maintained over a complete certification cycle of 3 years without major deviation from the norm in three external third-party audits. Thrombolysis rate significantly increased from 8·2% (2009) to 12·8% (2012). CONCLUSIONS: Certified quality management within a large stroke network using telemedicine is possible and might improve stroke care procedures and thrombolysis rates. Outcome studies comparing conventional stroke care and telestroke care are inevitable.

Quetiapine combined with amisulpride in schizophrenic patients with insufficient responses to quetiapine monotherapy.

OBJECTIVES: Treatment resistance often leads to combinations of second-generation antipsychotics. Well-designed trials evaluated add-on strategies involving clozapine, but also olanzapine and quetiapine (QTP) have pharmacodynamic properties that render supplementation with high-affinity antidopaminergic second-generation antipsychotics, for example, amisulpride (AMS), reasonable. METHODS: We report on 6 cases with partial response of psychotic positive symptoms to QTP despite sufficient dosage (mean, 783 mg/d) and serum levels (mean, 405 µg/L). Concomitant drug abuse and interfering pharmacological changes were excluded. RESULTS: The add-on of AMS in a mean dose of 466.7 mg/d (serum level, 132.1 µg/L) over a period of 8.3 weeks facilitated significant improvements of treatment-resistant psychotic symptoms. The Positive and Negative Syndrome Scale scores decreased from 94 to 54, whereas the Scale for the Assessment of Negative Symptoms and the Calgary Depression Scale for Schizophrenia significantly improved. Despite an increase in the mean body weight from 77.2 to 82.9 kg and an increase in prolactin levels from 43 to 163 µg/L, the observed general tolerance was good. CONCLUSIONS: The combination of AMS with QTP might be a successful strategy in individuals only partially responsive to quetiapine, but risks and benefits should be further evaluated in controlled clinical trials.