The Treatment Efficacy of Combination Atypical Antipsychotics With Sertraline in Patients With Schizophrenia

A randomized, double-blind trial of the treatment effect of dose-low antipsychotics combined with low-dose sertraline in 1640 schizophrenia patients

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: olanzapine-sertraline combination; Drug: only olanzapine; Drug: risperidone-sertraline combination; Drug: only risperidone; Drug: paliperidone-sertraline combination; Drug: only paliperidone; Drug: ziprasidone-sertraline combination; Drug: only ziprasidone

Detailed Description

OBJECTIVE: This study aimed to evaluate the treatment effect of combination low-dose antipsychotics with low-dose sertraline in 1640 schizophrenia patients

METHODS:

1. atypical antipsychotics and dose: including four atypical antipsychotics to form eight treatment groups: 1) olanzapine (7.5-10mg/day) combined with sertraline (50-100mg/day) group 2) only olanzapine (12.5-20mg/day) group 3) risperidone (2-3.5mg/day) combined with sertraline (50-100mg/day) group 4) only risperidone (4-6mg/day) group 5) paliperidone (3-4.5mg/day) combined with sertraline (50-100mg/day) group 6) only paliperidone (6-9mg/day) group 7) ziprasidone (60-100mg/day) combined with sertraline (50-100mg/day) group 8) only ziprasidone (120-160mg/day) group
2. blood biochemical examination: including blood routine examination, liver function, renal function, thyroid function, glucose and lipid level, prolactin, and related hormones and proteins
3. electrophysiological examination: including electrocardiograph, electroencephalography (EEG), and brain evoked potential
4. scale assessment: each patient was assessed by four clinical psychiatrists using the following scales: 1) psychopathology: positive and negative symptoms scale (PANSS) and clinical global impression scale (CGI-S) 2) emotional symptoms: Hamilton depression rating scale (HAMD) and Hamilton anxiety rating scale (HAMA) 3) social function: personal and social performance scale (PSP) 4) side-effect: treatment emergent side-effect scale (TESS) and rating sale for extrapyramidal side-effect (RESES)
5. blood drug concentration assay: including the drug concentration of olanzapine, risperidone, paliperidone, ziprasidone and sertraline, respectively
6. Weigh gain measurement: to measure height, weight for each patient

The above measurement data were collected at baseline, week4, week8, week 12 and week24.

• Study Type: Interventional
• Enrollment (Actual): 1640
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of schizophrenia by two senior psychiatrists
• Between 18 and 60 years and Han Chinese

Exclusion Criteria:

• A Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Axis I diagnosis other than schizophrenia
• Documented disease of physical diseases including, but not limited to seizure, epilepsy, aneurysm brain tumor, and stroke, dementia, parkinson's disease, Huntington's disease, multiple sclerosis
• Acute, unstable and/or significant and untreated medical illness (e.g., infection, unstable diabetes, uncontrolled hypertension)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: olanzapine-sertraline combination; the patient was prescribed low-dose olanzapine (7.5-10mg/day) combined with low-dose sertraline (50-100mg/day)	Drug: olanzapine-sertraline combination; the patient was prescribed low-dose olanzapine (7.5-10mg/day) combined with low-dose sertraline (50-100mg/day); Other Names: olanzapine-sertraline
Placebo Comparator: only olanzapine; the patient was prescribed moderate to severity dose of olanzapine (12.5-20mg/day)	Drug: only olanzapine; the patient was prescribed moderate to severity dose of olanzapine (12.5-20mg/day)
Experimental: risperidone-sertraline combination; the patient was prescribed low-dose risperidone (2-3.5mg/day) combined with low-dose sertraline (50-100mg/day)	Drug: risperidone-sertraline combination; the patient was prescribed low-dose risperidone (2-3.5mg/day) combined with low-dose sertraline (50-100mg/day); Other Names: risperidone-sertraline
Placebo Comparator: only risperidone; the patient was prescribed moderate to severity dose of risperidone (4-6mg/day)	Drug: only risperidone; the patient was prescribed moderate to severity dose of risperidone (4-6mg/day)
Experimental: paliperidone-sertraline combination; the patient was prescribed low-dose paliperidone (3-4.5mg/day) combined with low-dose sertraline (50-100mg/day)	Drug: paliperidone-sertraline combination; the patient was prescribed low-dose paliperidone (3-4.5mg/day) combined with low-dose sertraline (50-100mg/day); Other Names: paliperidone-sertraline
Placebo Comparator: only paliperidone; the patient was prescribed moderate to severity dose of paliperidone (6-9mg/day)	Drug: only paliperidone; the patient was prescribed moderate to severity dose of paliperidone (6-9mg/day)
Experimental: ziprasidone-sertraline combination; the patient was prescribed low-dose ziprasidone (60-100mg/day) combined with low-dose sertraline (50-100mg/day)	Drug: ziprasidone-sertraline combination; the patient was prescribed low-dose ziprasidone (60-100mg/day) combined with low-dose sertraline (50-100mg/day); Other Names: ziprasidone-sertraline
Placebo Comparator: only ziprasidone; the patient was prescribed moderate to severity dose of ziprasidone (120-160mg/day)	Drug: only ziprasidone; the patient was prescribed moderate to severity dose of ziprasidone (120-160mg/day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in psychopathology symptoms on PANSS during antipsychiatric treatment	The Positive and Negative Syndrome Scale (PANSS) is a well-characterized and widely applied dimensional assessment that reflects a balanced representation of positive and negative syndromes, their differential and general severity of illness. The scales not only measures positive and negative syndromes, but also suggests their differential and general severity of the illness. The items on the PANSS are defined with increasing levels from 1 to 7: 1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = moderate-severe, 6 = severe, and 7 = extreme. Then the PANSS score is totaled by sum up the ratings across different items, the potential range for positive and negative scales are from 7 to 49 whereas the General Psychopathology Scale is ranged between 16 to 112.	baseline, week 4, week 8, week 12, and week 24
changes in depressive symptoms on HAMD during antipsychiatric treatment	HAMD stands for Hamilton Rating Scale. It is the assessment that designed for examining the treatment significant of depression severity. The general format contains 17 items, 12 of them are scored from 0 to 4 while the rest of them ranges from 0 to 2. The items represented a variety of aspects: Depression mood, Feeling of guilt, Suicide, Insomnia early, Insomnia middle, Insomnia late, Work and activities, Motor retardation, Agitation, Psychic anxiety, Somatic anxiety, Somatic symptoms(gastrointestinal), somatic symptoms(general), Genital symptoms (sexual interest). Hypochondriasis, Weight loss and Insight. So A cut-off score less than or equal to 7 in the HAMD scale defines the symptomatic remission.	baseline, week 4, week 8, week 12, and week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in electroencephalography examination for brain activity during antipsychiatric treatment	electroencephalography, or EEG is the physiological method of choice to record the electrical activity generated by the brain via electrodes placed on the scalp surface. For faster application, electrodes are mounted in elastic caps similar to bathing caps, ensuring that the data can be collected from identical scalp positions across all respondents. By analysis of frequency and amplitude of five kind of brain waves(delta, theta, alpha, beta, gamma) , we could detect the synchronized activity of neurons within cortical areas even at sub-second timescales	baseline, week 4, week 8, week 12, and week 24

Collaborators and Investigators

• Sponsor: Beijing HuiLongGuan Hospital
• Investigators: Study Director: Xiaoe Lang, Doctor, The First Affiliated Hospital of Shanxi Medical University

Publications and helpful links

General Publications

• Mulholland C, Lynch G, King DJ, Cooper SJ. A double-blind, placebo-controlled trial of sertraline for depressive symptoms in patients with stable, chronic schizophrenia. J Psychopharmacol. 2003 Mar;17(1):107-12. doi: 10.1177/0269881103017001713.
• Ros LT. Treatment of postpsychotic depression with sertraline in patients with schizophrenia--own experience. Neuropsychopharmacol Hung. 2006 Oct;8(3):155-6.
• Poyurovsky M, Kurs R, Weizman A. Olanzapine-sertraline combination in schizophrenia with obsessive-compulsive disorder. J Clin Psychiatry. 2003 May;64(5):611. doi: 10.4088/jcp.v64n0518c. No abstract available.
• Bogers JPAM, Schulte PFJ, Broekman TG, Moleman P, de Haan L. Dose reduction of high-dose first-generation antipsychotics or switch to ziprasidone in long-stay patients with schizophrenia: A 1-year double-blind randomized clinical trial. Eur Neuropsychopharmacol. 2018 Sep;28(9):1024-1034. doi: 10.1016/j.euroneuro.2018.06.005. Epub 2018 Jul 17.
• Takekita Y, Koshikawa Y, Fabbri C, Sakai S, Sunada N, Onohara A, Nishida K, Yoshimura M, Kato M, Serretti A, Kinoshita T. Cognitive function and risperidone long-acting injection vs. paliperidone palmitate in schizophrenia: a 6-month, open-label, randomized, pilot trial. BMC Psychiatry. 2016 May 29;16:172. doi: 10.1186/s12888-016-0883-9.
• Shi H, Xu J, Lang X, Wu HE, Xiu MH, Zhang XY. Comparison of Efficacy and Safety Between Low-Dose Ziprasidone in Combination With Sertraline and Ziprasidone Monotherapy for Treatment-Resistant Patients With Acute Exacerbation Schizophrenia: A Randomized Controlled Trial. Front Pharmacol. 2022 Apr 26;13:863588. doi: 10.3389/fphar.2022.863588. eCollection 2022.
• Zhu C, Guan X, Wang Y, Liu J, Kosten TR, Xiu M, Wu F, Zhang X. Low-Dose Ziprasidone in Combination with Sertraline for First-Episode Drug-Naïve Patients with Schizophrenia: a Randomized Controlled Trial. Neurotherapeutics. 2022 Apr;19(3):1037-1046. doi: 10.1007/s13311-022-01242-7. Epub 2022 Apr 25.
• Chen YQ, Li XR, Zhang L, Zhu WB, Wu YQ, Guan XN, Xiu MH, Zhang XY. Therapeutic Response Is Associated With Antipsychotic-Induced Weight Gain in Drug-Naive First-Episode Patients With Schizophrenia: An 8-Week Prospective Study. J Clin Psychiatry. 2021 May 11;82(3). pii: 20m13469. doi: 10.4088/JCP.20m13469.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: July 14, 2019
• First Submitted That Met QC Criteria: August 29, 2019
• First Posted (Actual): September 3, 2019

Study Record Updates

• Last Update Posted (Actual): September 3, 2019
• Last Update Submitted That Met QC Criteria: August 29, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: schizophrenia; sertraline; olanzapine; risperidone; paliperidone; ziprasidone
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Olanzapine; Sertraline; Paliperidone Palmitate; Risperidone; Ziprasidone
• Other Study ID Numbers: CASPsy3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No