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ORIGINAL ARTICLE Table of Contents  
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The effect of cognitive behavioral therapy for insomnia on neuropsychological performance in schizophrenia patients with insomnia: A randomized controlled trial

1 Research Scholar, Department of Psychiatry, Shri Guru Ram Rai Institute of Medical and Health Sciences, Dehradun, Uttarakhand, India
2 Professor and Head, Department of Psychiatry, Shri Guru Ram Rai Institute of Medical and Health Sciences, Dehradun, Uttarakhand, India
3 Associate Professor, Department of Psychiatry, Shri Guru Ram Rai Institute of Medical and Health Sciences, Dehradun, Uttarakhand, India
4 Associate Professor, Department of Psychiatry, All India Institute of Medical Sciences, Bibinagar, Telangana, India

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Date of Submission27-Jul-2022
Date of Acceptance25-Sep-2022
Date of Web Publication05-Dec-2022


Background: Cognitive behavioral therapy for insomnia (CBT-I) is considered the gold standard for insomnia, but its relative role in improving cognition has not been addressed. Hence, we aimed to study the effect of CBT-I on sleep quality, psychopathology, and neuropsychological performance in schizophrenia.
Methods: Randomly allocated 40 right-handed schizophrenia patients with insomnia were delivered four sessions of weekly CBT-I. Pre-postassessments with Pittsburgh Sleep Quality Index (PSQI), AIIMS Comprehensive Neuropsychological Battery (AIIMS NCB), Positive and Negative Syndrome Scale, Multidimensional Fatigue Inventory, Warwick-Edinburg Mental Well-being Scale (WEMWBS), and Global Assessment Functioning (GAF) were done.
Results: CBT-I had significant effects on PSQI, AIIMS NCB total and memory scores, WEMWBS, and GAF compared to the control group.
Conclusion: In a subset of schizophrenia patients with insomnia, sleep-based interventions improve sleep quality and neuropsychological performance.

Keywords: Cognitive behavior therapy, neuropsychological tests, sleep qualities

How to cite this URL:
Pant K, Garg S, Mishra P, Tikka SK. The effect of cognitive behavioral therapy for insomnia on neuropsychological performance in schizophrenia patients with insomnia: A randomized controlled trial. Arch Ment Health [Epub ahead of print] [cited 2023 Mar 24]. Available from: https://www.amhonline.org/preprintarticle.asp?id=362703

  Introduction Top

Schizophrenia is being conceptualized as a neurocognitive disorder with its outcomes being understood based on cognitive impairments.[1] With evolving evidence, the role of sleep-in cognitive functions has changed from being passive to more active. As sleep macro- and microstructural abnormalities have been found in schizophrenia patients, a causal association between sleep and cognitive deficits has been hypothesized.[1],[2] Cognitive behavioral therapy for insomnia (CBT-I) is generally considered the gold standard for the treatment of insomnia.[3] It offers a more feasible, long-term, and acceptable selection than sleep medications in schizophrenia.[4] CBT-I offers reliable improvements in sleep (moderate-to-strong effect sizes)[5],[6],[7] while inconsistent effects on psychotic symptoms are seen.[5],[8] Moreover, the effectiveness of CBT-I over objective cognitive measures in schizophrenia has not been addressed.

With this background, we aimed to study the effect of CBT-I on sleep quality, psychopathology, and neuropsychological performance in schizophrenia subjects on a randomized rater-blinded placebo control design. An ancillary objective was to find out the CBT-I effects on concomitant mental being, quality of life, fatigue, and overall global assessment in schizophrenia subjects.

  Methods Top

Setting and study design

This study, a hospital-based randomized controlled trial was conducted at a tertiary care hospital and medical college in northern India. Participants were recruited from both inpatient and outpatient departments of the department of psychiatry. The study protocol was approved by the institute ethics committee (SGRR/IEC/23/21; IEC Registration No. ECR/710/Inst/UK/2015/RR-18). The study is registered in the CTRI (Clinical Trials Registry India, Number: CTRI/2020/09/036922). The total duration of the study was 3 months (October 2021 to January 2022). We enrolled patients for 1½ months. The follow-up period was 4 weeks (28 days).

Sample size

As per a previous study, the effect size of CBT-I in schizophrenia was found to be 0.33.[6] Thereby, targeting at least medium effect size and a power of 90%, the value of alpha error probability as 0.05, the number of groups being 2, and the number of measurements being 2, with a 25% dropout rate, for the statistical test being ANOVA: repeated measures, within and between interactions, the sample size in each group was estimated to be 20, making it a total sample size of 40. We used the G*Power tool for sample size estimation.


Right-handed patients in the age range from 18 to 59 years, meeting the diagnostic criteria for schizophrenia as per ICD-10 DCR,[9] sleep difficulties lasting 1 month or longer,[5] with a score of 5 or more on the Pittsburgh Sleep Quality Index (PSQI),[10] medication status unchanged for last 4 weeks,[5] and with the minimum 5 years of basic education were recruited. Exclusion criteria consisted of subjects with a seizure disorder, history of organicity, substance dependence except for nicotine and caffeine, a physical disability affecting the performance on neuropsychological assessment, and night shift workers who were excluded from the study. Patient enrolment was conducted by a doctorate student in clinical psychology.

A total of 75 patients were screened, out of which a total of 40 were enrolled for the treatment. Patients were randomly allocated to an active (CBT-I and treatment as usual [TAU]; Group A) and control group (TAU; Group B) with 20 patients in each group. A written and signed informed consent was taken from the patient and caregivers before enrolment. Out of 40, none of the patients dropped out of the study and all were included in the final analysis [CONSORT flow diagram: [Figure 1]].[11] Psychotropic medication status was unchanged for the entire duration of the study.
Figure 1: Flow diagram showing participants' recruitment. CBT-I: Cognitive behavioral therapy for insomnia, TAU: Treatment as usual

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Clinical variables and measures

Subjects were assessed for sleep quality, neuropsychological performance, and psychopathology at baseline and at the end of the 4th week (28th day). Furthermore, concomitantly fatigue, mental being, quality of life, and global functioning were assessed. Handedness to screen for right-handedness was assessed by the handedness preference schedule.[12] Sleep quality was assessed by the global score of PSQI.[10] The neuropsychological assessment was carried out by the All India Institute of Medical Science Comprehensive Neuropsychological Battery in Hindi Adult Form (AIIMS NCB).[13] AIIMS NCB consists of 13 basic scales, i.e. Motor Scale, Tactile Scale, Visual Scale, Receptive Speech Scale, Expressive Speech Scale, Reading Scale, Writing Scale, Arithmetic Scale, Memory Scale, Intellectual Processes Scale, Left Hemisphere Scale, Right Hemisphere Scale, Pathognomonic Scale, and Total Score Scale. Psychopathology was assessed through the Positive and Negative Syndrome Scale (PANSS).[14] Concomitant fatigue, mental well-being, quality of life, and global functioning were measured by the Multidimensional Fatigue Inventory,[8] Warwick-Edinburg Mental Well-being Scale (WEMWBS),[15] World Health Organization's abbreviated quality of life assessment (WHOQOL-BREF),[16] and Global Assessment Functioning (GAF).[17]

Sleep quality and neuropsychological functioning were the primary outcome variables, whereas psychopathology fatigue, mental well-being, quality of life, and global functioning were secondary outcome variables.


CBT-I was provided by a clinical psychologist. The core techniques standard for CBT-I were taken from three main sources.[12],[13],[14],[18],[19],[20] Text messages and telephone calls were conducted in between the sessions to sustain treatment thrust. CBT-I was given once a week, i.e., on 1st, 7th, 14th, and on 21st day, with a total of four sessions. Each session lasted for 45 min. Session 1 included goal formation, psychoeducation, sleep hygiene, winding down, stimulus control, and the establishment of a regular rising time. Session 2 included exploring the reason for tiredness, developing energy-generating strategies, education on use/misuse of bright light, reforming unhelpful beliefs about sleep, and strategies for nightmares. Session 3 included strategies to reduce the impact of low mood, intrusive thoughts, and hallucinations on sleep, addressing clock watching, cognitive restructuring, and brief relaxation. Session 4 included addressing the impact of medications and substance use on sleep, reviewing personal cycles of insomnia, stress management, and relapse prevention planning. Compliance with all four sessions was considered a minimum therapeutic dose.

Blinding procedure

The patients were randomly assigned to the two groups using blocks of random-number sequences; the block size was 4. The numbers were written in sealed opaque envelopes for concealment. The envelope for each patient was opened after the initial screening for eligibility and before the commencement of either CBTI or TAU. The assessments on various rating scales and neuropsychological test batteries at baseline and posttreatment were coded and conducted by a rater who was blind to the randomization and treatment allocation. Retrospectively, the rater was made to guess the treatment arm for the study participants based on their pre-and postsleep quality scores. The guess matrix resulted in a Cohen's kappa coefficient of −0.02, which implied "no agreement" and therefore indicating good integrity of the rater blinding.

Statistical analysis

Study data were analyzed using SPSS (version 28). The assumption of normality was tested by normal probability plots and the Kolmogorov-Smirnov test. Group differences were examined with an independent t-test and Chi-square (wherever applicable). Continuous variables that failed the assumption of normality were compared by applying the Mann-Whitney U-test. Within-group pre-post analysis for each Group A and B was conducted using paired sample t-test and Wilcoxon signed-rank test (wherever applicable). The overall effect of treatment over time for the two groups was analyzed using mixed model Analysis of Variance (ANOVA) with treatment (Group A and Group B) as the between-subject factor and time (baseline and at end of the 4th week i.e., 28th day [postintervention]) as the within-subject factor. To control for baseline differences, baseline scores were included as covariates (wherever applicable). For comparison of group × time interaction over AIIMS NCB total scores, age of onset, baseline PANSS-total scores, and chlorpromazine (CPZ) equivalents were included as covariates.

  Results Top


A total of 75 patients were screened, out of which a total of 40 were enrolled for the treatment. Patients were randomly allocated to an active (CBT-I and TAU; Group A) and control group (TAU; Group B) with 20 patients in each group.

Descriptive data

Both Group A and Group B subjects had comparable proportions of gender, marital status, habitat, socioeconomic condition, occupation, family history, and history of substance dependence. Subjects randomized to "Group A" and "Group B" were comparable on age (t[38] =0.374, P = 0.711), age at onset of illness, and CPZ equivalent dose of last trial (t[38] =1.103, P = 0.523) [Table 1].
Table 1: Comparison of sociodemographic and clinical variables across the group's A and B (n=40)

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Clinical measures

All baseline clinical variables except WEMWBS (t = −2.816; P = 0.008), WHOQOL-BREF (t = 2.509; P = 0.016), GAF Scale (t = 2.300; P = 0.027), and Tactile Scale (t = 2.705; P = 0.010) were comparable between Group A and Group B [Supplementary Table 1[Additional file 1]]. Within the group (Group A) analysis except for writing, pathognomic subscale, and WHOQOL-BREF, all the other clinical measures did show significant improvement with CBT-I [Table 2]. However, when compared for the effects of time (from baseline and at end of the 4th week) across the two groups (group × time interaction) as per-protocol analysis, the mixed model repeated measures ANOVA except for PSQI (F = 30.025; P ≤ 0.000), memory (F = 11.962; P = 0.001), AIIMS NCB total scores (F = 4.791; P = 0.035), WEMWBS (F = 5.062; P = 0.030), and GAF (F = 4.355; P = 0.044), other clinical measures did not find a significant group × time effect. There were no complaints about therapy and no adverse events were reported.
Table 2: Interaction effect of intervention between Group A and Group B across pretreatment phase (baseline; precognitive behavioral therapy for insomnia) and posttreatment (end of 4th week; postcognitive behavioral therapy for insomnia) using mixed model analysis (n=40)

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  Discussion Top

We are among the first to study the effect of CBT-I on sleep quality, psychopathology, and neuropsychological performance in schizophrenia with insomnia in a randomized rater blinded control design. In comparison to the control (TAU) group, CBT-I improved sleep quality and neuropsychological performance specifically memory. Additional benefits on mental well-being and global functioning were found.

Differential response to CBT-I to variable outcomes supports the findings of Freeman et al.(2015) and Water et al. (2020). Freeman et al. (2015) found a large effect size of CBT-I (6 sessions) over insomnia at 12 weeks with variable effects on psychosis. Water et al. (2020) categorized CBT-I responders (strong, partial, and poor) and stressed the role of client-elicited treatment goals.

There is preliminary evidence for at least moderate effects of CBT-I on subjective measures of cognitive functioning in the nonpsychotic population.[21] However, there is a dearth of studies on the effects of CBT-I on objective cognitive measures.[21] Improved neuropsychological performance due to CBT-I has been potentially attributed to reversible sleep-dependent memory deficits.[22] This improvement in sleep-dependent memory consolidation is could be related to potentially modifiable sleep spindles deficits in schizophrenia.[1],[23]

While studying the effects of CBT-I on neuropsychological performance in schizophrenia is a distinction, there were important limitations such as the short-term duration of the trial, no further follow-up assessments, and lack of characterizing sleep architecture (through polysomnography). Drug compliance was not assessed and it is another important limitation. The effects of multiple comparisons (primary and secondary outcome variables) were included for the prior sample size estimation and this might have led to an underestimation of the sample size. Due to the relative modest sample size, the generalizability of the findings is limited.

  Conclusion Top

In summary, we conclude that in a subset of schizophrenia patients with insomnia, sleep-based interventions (CBT-I) improve sleep quality and neuropsychological performance.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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Correspondence Address:
Shobit Garg,
Shri Guru Ram Rai Institute of Medical and Health Sciences, Dehradun - 248 001, Uttarakhand
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/amh.amh_116_22


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  [Table 1], [Table 2]


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