Journal Article Annotations
2019, 1st Quarter


Annotations by Sahil Munjal, MD
March 2019

  1. Comparative Efficacy of Therapies for Treatment of Depression for Patients Undergoing Maintenance Hemodialysis: A Randomized Clinical Trial.
  2. Muscle Relaxant Use Among Hemodialysis Patients: Prevalence, Clinical Indications, and Adverse Outcomes
  3. Chronic kidney disease in adults with schizophrenia: A nationwide population-based study.

PUBLICATION #1 — Psychonephrology
Comparative Efficacy of Therapies for Treatment of Depression for Patients Undergoing Maintenance Hemodialysis: A Randomized Clinical Trial.
Mehrotra R, Cukor D, Unruh M, Rue T, Heagerty P, Cohen SD, Dember LM, Diaz-Linhart Y, Dubovsky A, Greene T, Grote N, Kutner N, Trivedi MH, Quinn DK, Ver Halen N, Weisbord SD, Young BA, Kimmel PL, Hedayati SS.


Type of study:Randomized Clinical Trial

The finding: The authors tested 2 hypotheses among patients receiving maintenance hemodialysis (HD) who had major depressive disorder (MDD) or dysthymia, as defined by the DSM. Phase 1 of the study investigated whether an engagement interview would increase the frequency of depression treatment. Phase 2 compared the efficacy of CBT vs sertraline over 12 weeks of therapy. Quick Inventory of Depressive Symptoms–Self-Report (QIDS-SR) was used as an assessment tool in both groups. 

In phase 1, evaluation was conducted face to face by trained therapists while patients received outpatient HD. Motivational interviewing was done to help participants articulate their ambivalence about treatment and echoed back to patients their expressions of wanting life to be different. Also, a 20 min DVD was given to improve their understanding of depression and its treatment. Control group had a visit from a research team member during which they discussed the diagnosis and treatment options within and outside the study.

In Phase 2 ( CBT vs sertraline), participants assigned to the CBT group were scheduled for 10 sessions of 60 minutes each over 12 weeks( same therapist) while they received HD. Therapy included standard components of the intervention (psychoeducation, behavioral intervention, cognitive intervention, and health behavior modification (adherence to dialysis and challenging disease-specific cognitive distortions and maladaptive thought patterns).

The sertraline group participants had their dosage titrated individually every 2 weeks for the first 6 weeks and then maintained for 6 weeks in accordance with measurement-based care (target dose was 200mg unless adverse effects).

Findings concluded an engagement interview had no effect on patients’ acceptance of depression treatment. Depressive symptoms and several other patient-reported outcomes (perception of disability and satisfaction with life, energy and vitality, and sleep) improved with both CBT and sertraline therapy with 29% and 40% respectively, achieving remission (QIDS-C score <5).  But, the outcome scores at 12 weeks were modestly better for the sertraline group. Third, adverse events occurred more frequently in the sertraline than the CBT group.

Strength and weaknesses: Strengths- It was an open-label, randomized controlled trial, parallel-group, multicenter (at 3 clinical sites in metropolitan areas in different states), and thereby enhancing external validity. Patients were systematically screened for depression. Adherence was strong, loss to follow-up was infrequent (5%), and patient-reported outcomes were ascertained by trained off-site personnel blinded to treatment assignment. It was the first study to test the comparative efficacy of CBT and antidepressant drugs in this population.

Weaknesses- It did not look into whether any treatment (CBT vs sertraline) was superior to placebo or no treatment. The effect size was modest, and it is unclear whether the differential efficacy is clinically meaningful. It did not test for persistence of effect after 12 weeks of treatment.

Relevance: About a third of patients with end-stage renal disease who are receiving maintenance HD have depressive symptoms. It contributes to poor quality of life, adhering to diet, medications, treatment schedules, navigating care transitions, greater health care use and higher mortality rates. Many of these patients do not receive treatment, perhaps because of their reluctance to accept the diagnosis or treatment. Also, evidence for the efficacy of antidepressant therapies in this population is limited. Although CBT has demonstrated therapeutic efficacy, SSRI’s including fluoxetine, escitalopram and sertraline have had inconsistent results. The study, first of its kind showed that an engagement interview had no effect on depression treatment acceptance. A high proportion of patients (two thirds of patients in each group) began treatment within 28 days which may be due to making depression treatment available to patients during their HD. The study also showed positive benefit of both CBT and Sertraline. Sertraline was modestly superior which may be due to it targeting the somatic symptoms of depression. Also, the high disease burden along with the cognitive deficits may limit the patients to be fully engaged in CBT. This study points the clinician to facilitate individualized patient and provider decisions on options for treating depression in HD patients.

PUBLICATION #2 — Psychonephrology
Muscle Relaxant Use Among Hemodialysis Patients: Prevalence, Clinical Indications, and Adverse Outcomes
Mina D, Johansen KL, McCulloch CE, Steinman MA, Grimes BA, Ishida JH.


Type of study: Observational cohort study.

The finding: The study aimed to describe the prevalence of muscle relaxant use and adverse outcomes in hemodialysis patients (HD).

It was a retrospective cohort study which included adults receiving maintenance HD using clinical and billing data during 2011, which included the Part D prescription drug file, in the US Renal Data System (USRDS). Outcome variables were first episode of altered mental status, fall, and fracture requiring an emergency department visit or hospitalization.

In the study, the prevalence of muscle relaxant prescription was high (10%) during that year which is much higher in the general US population (1%-3%). Muscle relaxant that was used most commonly was cyclobenzaprine.  Musculoskeletal pain and muscle spasticity were the most common diagnoses associated with the use. Their use was associated with higher risk for altered mental status (AMS) and falls. Study could not rule out a clinically meaningful association between its use and fracture and did show a lower risk of death which may be due to residual confounding.

Strength and weaknesses: Strengths- The study had a large sample size, which is reflective of the US HD population. There was detailed medication data, which led the authors to model time-varying muscle relaxant exposure.

Weaknesses- Muscle relaxant use was determined using claims data, therefore it is hard to ascertain that patients took their medications, exact period of use, medications were taken on a scheduled or as-needed basis, proper ICD-9/ CPT codes were used. It was an observational study, therefore casual association between muscle relaxant use and adverse outcomes cannot be inferred. There may have been potential unmeasured confounders (eg, hypotension and frailty). The study did show a lower hazard of death in patients taking these agents which may reflect residual confounding (eg, healthier people may be more likely to receive a prescription for a muscle relaxant) or reverse causality (eg, people with terminal illness may be less likely to receive a muscle relaxant), or lack of reliable capture of muscle relaxant use before death.

Relevance: There is a paucity of data to guide the use of muscle relaxants in HD patients. They include antispasmodics such as cyclobenzaprine which are indicated for spasms in the context of acute musculoskeletal disorders (eg, neck or back pain), and antispastics such as baclofen, tizanidine, and dantrolene which are indicated for spasticity due to upper motor neuron disorders. They are commonly used in the US and associated with significant side effects including drowsiness and sedation, increased risk for AMS, fall, and fracture among older adults which were also reported in this study. HD patients are particularly predisposed to these side effects due to existing risk factors for falls and fractures, including dialysis-related hypotension, frailty, and chronic kidney disease–mineral and bone disorder (CKD-MBD). It should also be noted that these agents or their metabolites may build up in the setting of decreased kidney function.

Clinicians are advised to avoid the use of baclofen, because it is primarily eliminated by renal excretion, unlike other muscle relaxants including cyclobenzaprine which is mostly hepatically cleared (therefore commonly prescribed in this cohort.  

It is important to take into consideration that currently data is insufficient to make definitive recommendations about whether and how to use muscle relaxants in HD patients. It may be reasonable in some patients, where their use may improve quality of life at the expense of higher hospitalization rates or other complications, including AMS and falls.

PUBLICATION #3 — Psychonephrology
Chronic kidney disease in adults with schizophrenia: A nationwide population-based study.
Tzur Bitan D, Krieger I, Berkovitch A, Comaneshter D, Cohen A


Type of study: Observational cohort study.

The finding: The study aimed to assess the association between schizophrenia and chronic kidney disease (CKD) along with accessibility to dialysis and kidney transplantation. The study used Health Services databases and looked at 27,516 patients diagnosed with schizophrenia and an equal number of age and sex frequency-matched controls. The study found that schizophrenia diagnosis was associated with a higher risk for CKD, even when controlling for known risk factors. Also, these patients were less likely to receive treatments for CKD, such as dialysis and kidney transplantation. Further, schizophrenic patients were not diagnosed at early stages compared to the control group with respect to their kidney problems.

Strength and weaknesses: Strengths- Study had a nationwide population-based cohort design. It had a high validity achieved through logistic checks such as comparisons of diagnoses from various sources and by direct validation of the diagnoses by the treating physicians of each patient. Also, 10% of the cohort had their clinical files evaluated and confirmed if they would meet ICD criteria for a diagnosis of schizophrenia.

Weaknesses- Study design was cross-sectional; therefore, causal direction cannot be ascertained. It did not assess the usage of antipsychotic medications as a possible predictor of CKD. They study population was in Israel, applicability in other countries may be difficult to ascertain.

Relevance: As we know, CKD is commonly associated with adverse clinical outcomes, poor quality of life and high health-care utilization.  There has been increasing evidence indicating substantial disparities in healthcare provision to patients with SMI, which in turn contributes to poor physical health outcomes for these patients. Patients with schizophrenia are at an elevated risk for CKD, given diabetes, hypertension, smoking and obesity are highly prevalent in this population.  Study findings showing lower probability to receive dialysis care and renal transplant converges with previous reports indicating patients with schizophrenia receive suboptimal pre-dialysis renal care. This may be due to potential drug interactions, fear of low compliance with medication and medical follow-up after transplant, poor social support needed to handle post-transplant rehabilitation, and assumed emotional and cognitive disabilities which might affect the management of the medical issues associated with the transplant. Clinicians may consider routine monitoring of renal function in patients with schizophrenia to facilitate early identification of renal damage and thus minimize long-term adverse outcomes.