Prevalence and clinical corelates of metabolic syndrome in patients receiving modified electro-convulsive therapy: An exploratory study from North India

Abstract

Background:

Modified electroconvulsive therapy (mECT) is the treatment of choice in suicidality and resistant psychiatric disorders like treatment resistant depression and schizophrenia. A handful of studies with modest sample sizes have shown some effect of mECT on glycemic control and cholesterol levels; however, not a single study has explored the association between mECT and metabolic syndrome.

Aim:

To find out the prevalence and clinical corelates of metabolic syndrome in patients receiving mECT.

Materials and Methods:

This was a cross-sectional exploratory study in which 89 patients receiving mECT were recruited via systematic random sampling and evaluated for metabolic syndrome by using modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III) criteria.

Results:

The prevalence of metabolic syndrome in patients receiving mECT was 55.06%. The most common metabolic abnormality noted was elevated blood pressure, with increased diastolic blood pressure in 71.9% and elevated systolic blood pressure in 67.42%. We found a significant association between age (P < 0.001) and gender of patients on ECT with metabolic syndrome. (P = 0.019). Having received mECT’s in past (P < 0.001) and a higher number of mECTs (P < 0.001) were both significantly associated with metabolic syndrome. Multivariate logistic regression metabolic syndrome was significantly predicted by the number of mECTs [{(unadjusted odds ratio 1.57), (adjusted odds ratio 1.52)}(P value < 0.001)}].

Conclusion:

Our findings revealed an increased prevalence of metabolic syndrome in mECT population; this emphasizes the importance of screening for metabolic syndrome to reduce the risk of cardiovascular disease and premature death.

Metabolic syndrome (MetS) is a complex disorder characterized by the presence of interrelated risk factors of metabolic origin that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD), type 2 diabetes, and stroke. This disorder has a constellation of metabolic abnormalities which include abnormal glucose metabolism (type 2 diabetes, impaired glucose tolerance, or altered fasting glycemia) central obesity, atherogenic dyslipidemia, low HDL cholesterol, and hypertension.[1,2]

Patients with psychiatric illness have shown a higher prevalence of metabolic syndrome, when compared with general population.[3] Apart from insulin resistance, various other factors like psychological stress, excessive smoking, lack of exercise, poor diet, excessive caloric consumption, and inadequate medical care have been implicated in the higher prevalence of MetS among psychiatric patients.[4] Co-occurrence of MetS with mood disorder not only aggravates the clinical course but also increases the risk for depressive episodes and suicidality and also leads to a 10- to 20-year shortening in life expectancy.[5] Thus, it is a challenge affecting the health care system. Moreover, compared with euglycemic patients, those with comorbid bipolar disorder and type 2 diabetes or insulin resistance have significantly higher risk of rapid cycling, chronic course, and treatment refractory course.[5,6,7]

mECT is the recommended treatment modality for resistant or refractory psychiatric disorders like treatment-resistant depression, bipolar disorder, schizophrenia, affective disorders, suicidality, and catatonia.[4,8] The exact mechanism of action of mECT is not known, but its multimodal action on neurotransmitters, hormones, as well as neuropeptides has been widely studied.[9] mECT leads to a decline in the levels of growth hormone in patients of schizophrenia and corticotropin-releasing hormone in cerebrospinal fluid of patients with depression. On the other hand, it enhances the levels of thyroid-stimulating hormone (TSH), prolactin, plasma cortisol, and neuropeptide Y.[8]

The effect of mECT on the levels of plasma noradrenaline is controversial. It has been found to decrease plasma noradrenaline in patients with melancholic or psychotic depression and increase in those with nonmelancholic depressive mood state.[10]

Also, the impact of mECT on blood glucose is nonconclusive. In one study, patients have achieved glycemic control post-mECT in diabetic patient.[11] However, in another study, no such increase was noted.

Thus, there are several reasons for conducting the present study. First of all, there are contradictory reports about the possible effects of mECT on the blood glucose level and noradrenaline levels, which in-turn might affect blood pressure. Only a handful of studies[11,12,13,14] with small sample sizes suggest some changes in metabolic parameters in patients receiving mECT. However, to our knowledge, no study has assessed metabolic syndrome in patients on mECT. It is necessary to determine metabolic derangements, prevalence of metabolic syndrome, and investigate the clinical corelates in patients receiving modified electro-convulsive therapy.

MATERIALS AND METHODS

This was a cross-sectional, exploratory, hospital-based study conducted at the Institute of Mental Health and Neurosciences Kashmir from December 2024 to May 2024.

Patients aged 18 and above, currently receiving mECT in the hospital, were included in the study. Those receiving multiple sessions were assessed only for the first time. Pregnant and postpartum females were excluded from the study. Ethical clearance was obtained from the Institutional Review Board (approval number: IRBGMC/PSY365, dated 29/11/23). The study instruments used were semistructured sociodemographic proforma and modified national cholesterol education program adult treatment panel III (NCEP ATP-III) criteria.[1] Patients were assessed for the presence of metabolic syndrome, as per the modified NCEP ATP-III criteria for the Asian population, which is an important research tool used widely by the physicians in India and world over. As per the criteria, the presence of three or more of the following are necessary for the diagnosis of metabolic syndrome: increased waist circumference (>90 cm for males and >80 cm for females), elevated triglycerides (≥150 mg/dl or on lipid lowering agents), low HDL (<40 mg/dl for males and <50 mg/dl for females), elevated blood pressure (≥130/85 mmHg), and increased fasting glucose (≥100 mg/dl or on oral hypoglycemic medications or insulin.)

Modified Electroconvulsive therapy

As per the mECT unit protocol, patients were treated with brief pulse (0.5–1 ms) ECT delivered by a Thymatron System IV device (Somatics, Lake Bluff, IL, USA) using a bitemporal electrode. Anesthesia was induced with intravenous propofol, and succinylcholine (0.5 mg/ kg) was used as a muscle relaxant.[15] The psychotropic medications were maintained unchanged throughout the mECT treatment course.

Information about past and current medical or psychiatric history was gathered through clinical interview of the patient or the accompanying attendant and by reviewing the medical records. Waist circumference was measured in centimeters using a measuring tape. It was measured in a horizontal plane, at a point midway between the inferior costal margin and the superior iliac crest, at the end of normal expiration, while the patient was standing. These measurements were repeated twice, and an average was taken.[16]

For measuring systolic and diastolic blood pressure, a standard mercury-based sphygmomanometer with a cuff size of 14 × 54 cm was used. Resting BP was measured in the morning, while the patient was in a seated position in a quiet room after 10 minutes of rest. Two BP readings at 2-min intervals were taken using the auscultatory method. The mean BP of the two recorded measurements was taken.[17]

Baseline measurement of triglycerides, HDL, and fasting plasma glucose at room temperature was obtained. For all the inpatients, the blood samples were taken as a part of the routine admission procedure; however, for those who visited the out-patient department, blood investigations were considered valid if done within 2 months of study entry, and otherwise, patients were asked to get it done within a week of study entry.[18] Blood sampling was done after 10–12 hours of overnight fasting; patients who did not fast were rescheduled. Analytes were assessed on the Cobas C-50 1 equipment (Roche Diagnostics, Switzerland) using kits provided by the manufacturer. HDL and triglycerides were analyzed by a homogenous calorimetric enzymatic method.[19] Plasma glucose was assessed using glucose oxidase peroxidase enzymatic assay on Hitachi 912, Japan. Intra and interassay variations were within the limits by the manufacturer.[20]

Statistical Analysis: Categorical variables were summarized as percentages and the five-number summary was used to summarize the number of mECT sessions received by the patients. The relationship between metabolic syndrome, sociodemographic and other categorical variables were analyzed using the exact test. The two-sample Wilcoxon rank-sum test was used to analyze the relationship between number of ECT sessions and metabolic syndrome. Unadjusted and adjusted odds ratios for all variables which were significantly associated with metabolic syndrome were reported. The history of ECT was not included in the multivariable model because of failure to converge. We report two-sided P values and considered P < 0.05 as statistically significant. Data analysis was performed using Stata version 17.

RESULTS

A total of 89 patients were recruited in the study after fulfilling inclusion and exclusion criteria. The mean age of the sample was 36.44 ± 12.29 with slight male predominance who constituted 52.81% of the sample. The median number of mECTs received was 6 with an interquartile range of 4 to 12. Complete sociodemographic and clinical profile are presented in Tables 1 and 2, respectively.

Table 1.

Sociodemographic profile

Variable	n=89 Mean±SD/frequency (%)
Age     <30 years     30-50 years     >50 years	38 (42.70) 36 (40.45) 15 (16.85)
Gender     Male     Female	47 (52.81) 42 (47.19)
Education     No formal education     Secondary education     Senior secondary education     Graduate     Postgraduate	18 (20.22) 39 (43.82) 20 (22.47) 11 (12.36) 1 (1.12)
Occupation     Unemployed     On paid employment     Homemaker     Owner of business     Professional	19 (21.35) 23 (25.84) 34 (38.20) 9 (10.11) 4 (4.49)
Socioeconomic status     Upper middle     Lower middle     Upper lower     Lower     Upper class	30 (33.71) 26 (29.21) 16 (17.98) 11 (12.36) 6 (6.74)

Table 2.

Clinical profile of participants

	n (%)
Psychiatric diagnosis     Major depressive disorder     Bipolar depression     Bipolar disorder, Mania     Catatonia     Treatment resistant schizophrenia     Active suicidality     Othersa	26 (29.21) 19 (21.35) 15 (16.85) 12 (13.48) 7 (7.87) 5 (5.61) 5 (5.61)
Receiving Mood stabilizers     Lamotrigine     Valproate+Lithium     Lithium+lamotrigine     lithium     valproate	60 (67.41) 17 (19.10) 14 (15.73) 13 (14.61) 10 (11.24) 6 (6.74)
Receiving Antipsychotics     Olanzapine     Quetiapine     Amisulpride     Aripiprazole     Clozapine     Othersb	73 (82.02) 23 (25.84) 14 (15.73) 11 (12.36) 11 (12.36) 9 (10.11) 5 (5.61)
receiving Antidepressantsc	42 (47.20)
Previous mECT     Yes     No	49 (55.05) 40 (44.94)
Median number of mECT sessions received	6 (inter-quartile range 4-12)

^aTreatment-resistant schizoaffective disorder (n=1), Parkinson’s diseases (n=1), seizure disorder (n=1), OCD (n=2). ^bRisperidone (n=4), cariprazine (n=1). ^cMirtazapine (n=10), sertraline (n=10), escitalopram (n=10), fluoxetine (n=5), desvenlafaxine (n=4), and venlafaxine (n=3)

The prevalence of metabolic syndrome in patients receiving mECT was 55.06% as per modified NCEP ATP-III criteria. The mean and standard deviation of individual metabolic parameters are depicted in Table 3. The population pyramid frequency of different variables in those with and without metabolic syndrome is depicted in Figures 1 and 2.

Table 3.

Metabolic parameters

Metabolic parameter	Mean±SD
Waist circumference	91.49±8.68
Triglycerides	178.62±70.18
HDL	62.10±40.15
LDL	102.88±31.38
Blood sugar fasting	92.94±12.60
Systolic blood pressure	131.30±10.83
Diastolic blood pressure	89.71±10.14

Figure 1.

The population pyramid frequency of Triglycerides in those with and without metabolic syndrome

Figure 2.

The population pyramid frequency of waist circumference in those with and without metabolic syndrome

On comparing the sociodemographic profile of patients with and without metabolic syndrome, patients with metabolic syndrome were significantly older than patients without metabolic syndrome (41.84 ± 12.46 Vs 29.82 ± 8.27; P < 0.001). As shown in Table 4, females receiving mECT were more likely to have metabolic syndrome, in comparison with males.

Table 4.

Relationship of metabolic syndrome with sociodemographic in mECT population

Variable	Subjects with MetS (n=49) mean±SD/frequency (%)	Subjects without MetS (n=40) mean±SD/frequency (%)	t test/Chi square P value
Age	41.84 (±12.46)	29.82 (±8.27)	<0.001
Age     <30     31 – 50     >51	12 (31.58) 24 (66.67) 13 (86.67)	26 (68.42) 12 (33.33) 2 (13.33)
Gender     Male     Female	20 (42.55) 29 (69.05)	27 (57.45) 13 (30.95)	0.019
Education     No formal education     Secondary education     Senior secondary education     Others	10 (55.56) 26 (66.67) 7 (35.00) 6 (50.00)	8 (44.44) 13 (33.33) 13 (65.00) 6 (50.00)	0.131
Occupation     On paid employment     Unemployed     Home-maker     Others	16 (69.57) 7 (36.84) 20 (58.82) 6 (46.15)	7 (30.43) 12 (63.16) 14 (41.18) 7 (53.84)	0.267
Socioeconomic status     Upper middle     Lower middle     Upper     Upper Lower     Lower	19 (63.33) 19 (73.08) 2 (33.33) 5 (31.25) 4 (36.36)	7 (26.92) 11 (36.67) 4 (66.67) 11 (68.75) 7 (63.64)	0.030

We found that patients with metabolic syndrome had received significantly higher number of mECT sessions. Similarly, those who had received mECT sessions previously, were more likely to have metabolic syndrome compared with those who were receiving mECT sessions for the first time. Complete relationship of metabolic syndrome with sociodemographic and clinical profile is presented in Tables 4 and 5.

Table 5.

Relationship of metabolic syndrome with clinical variables in mECT population

Variable	Subjects with MetS (n=49) mean±SD/frequency (%)	Subjects without MetS (n=40) mean±SD/frequency (%)	t test/Chi square P value
Psychiatric diagnosis
Major depressive disorder	16 (61.54)	10 (38.46)	0.114
Bipolar disorder, Mania	12 (80.00)	3 (20.00)
Bipolar disorder, Depression	8 (42.11)	11 (57.89)
Active suicidality	2 (40.00)	3 (60.00)
Catatonia	4 (33.33)	8 (66.67)
Treatment-resistant schizophrenia	4 (57.14)	3 (42.86)
Others	3 (60.00)	2 (40.00)
Receiving Mood stabilizers (n=60)
Yes     No	32 (53.33) 17 (58.62)	28 (46.67) 12 (41.38)	0.657
Receiving Antipsychotics (n=73)
Yes     No	41 (56.16) 8 (50.00)	8 (50.00) 8 (50.00)	0.783
Receiving Antidepressants (n=42)
Yes     No	27 (64.29) 15 (35.71)	22 (46.81) 25 (53.19)	0.135
Daily valproate dose >1g	13 (76.47)	4 (23.53)	0.567
Previous mECT
Yes     No	46 (93.88) 3 (6.12)	3 (7.50) 37 (92.50)	<0.001
Median number of mECT sessions received	11 (inter-quartile range 7-14)	4 (inter-quartile range 3-5.5)	<0.001

Multivariate logistic regression analysis was used to assess the predictors of metabolic syndrome. All variables which had significant difference in the comparison analysis with a P value less than 0.05 were considered and analyzed. As depicted by Table 6, the presence of metabolic syndrome was significantly predicted by the number of mECT sessions (P < 0.001).

Table 6.

Multivariate logistic regression analysis

Variable	Odds ratio (OR)	P	95% confidence interval	Corrected odds ratio	P	95% confidence interval
Age
<=30 years     31-50 years     >50 years	Ref 4.33 14.08	- 0.003 0.002	- 1.64-11.47 2.74-72.48	Ref 2.96 6.65	- 0.102 0.054	- 0.81-10.87 0.97-45.56
Gender
Male     Female	Ref 3.01	- 0.013	- 1.26-7.1	Ref 2.06	- 0.28	- 0.56-7.61
Socio-economic status
Middle     Upper     Lower	Ref 0.24 0.24	- 0.114 0.004	- 0.004-1.42 0.009-0.63	Ref 0.61 0.57dr	- 0.677 0.427	- 0.006-6.34 0.14-2.28
Previous mECT
No     Yes	Ref 189.1	- <0.001	- 36.04-992.41	-	-	-
Number of mECT sessions	1.57	<0.001	1.30-1.91	1.52	<0.001*	1.24-1.88

*statistically significant

DISCUSSION

To the best of our knowledge, no study until date has explored the prevalence of metabolic syndrome in patients receiving modified electroconvulsive therapy. The present study found a prevalence of 55.06% in patients on mECT. Prevalence in other studies conducted all across the globe was found to range from 25% to 40%.[18,21,22] In a hospital-based cross-sectional study conducted among patients with psychiatric disorders in Saudi Arabia, the prevalence of metabolic syndrome was found to be equal to 41.5%.[23] In a study from India, the prevalence as per NCEP ATP III in patients with a diagnosis of schizophrenia was found to be equal to 44.5%,[24] while as 41% of patients of bipolar disorder fulfilled the criteria for metabolic syndrome.[25]

Compared with previous studies, our study had some different findings; we found higher rates of metabolic abnormalities as compared with prior studies. Previous studies have documented increased waist circumference[24] or raised triglycerides[23] as the most frequent metabolic derangement. In one study conducted in Saudi Arabia, increased waist circumference was found in 42.2% of patients; elevated triglycerides were found in 32.8% of patients.[23] We found elevated blood pressure (systolic 71.9%; diastolic 67.42%) as the most common metabolic derangement in our study population.

We found the prevalence of hypertriglyceridemia to be 65.17%, abdominal obesity to be 44.94%, and elevated fasting sugar to be 23.60%. As per a study done in India in patients of schizophrenia, abdominal obesity was the most frequent metabolic abnormality, endorsed in about 64.8% of patient, while as elevated fasting blood sugar was present in just 15.9% of the patients.[24] An association between female gender receiving mECT and metabolic syndrome. However, previous studies that have assessed the variability of metabolic syndrome and sociodemographic parameters have reported either a female gender preponderance[23,26] or a male gender preponderance[27] or no association with gender at all.[21,28] We also found an association between socioeconomic status and metabolic syndrome in mECT receiving population. As per one study, metabolic syndrome was more likely in those with advanced age, illiterate, and with longer duration of psychiatric illness.[23] Advanced age more than 35 years, female gender, residing in an urban area, and being employed was found to be significant predictors of metabolic syndrome in an Indian study.[24]

The highlight of the study was that we found a significant association between course of mECT’s received in past and a positive correlation was found between number of mECT sessions received and metabolic syndrome. The findings of our study can be explained by the direct effect of mECT on the brain by the interaction of HPA axis and mECT or the multimodal action of mECT through its interaction with serotonin, ghrelin, leptin, and cholesterol.[12,29] The increase in BP occurs due to increased cardiac workload from increased sympathetic and parasympathetic activity.[30,31] Furthermore, some studies have reported an escalation in the levels of circulating catecholamines almost fifteen times that of the basal values as soon as the electrical impulse is triggered during mECT. We did not aim to determine the mechanism of the cardiovascular alterations during mECT; however, the elevation in BP noted in our study population seems to be in concordance with those reported in literature and can be explained by the sympathetic hyperactivity and direct effect of mECT.[30,31,32]

In one study on acute metabolic effects following mECT, it was found that cholesterol levels and glucose levels increase 20 minutes post-mECT.[4,8] ECT may increase glucose levels via cortisol, norepinephrine, or insulin.[4] Though some studies reported an elevation in mean serum cholesterol levels after mECT, however, the mechanism linking ECT and changes in blood lipids remains unknown.[4,12]

Limitations

This was an exploratory study with a cross-sectional design; hence, causality cannot be inferred. We did not calculate the sample size before conduct of study. Concomitant use of psychotropic medications like mood stabilizers and antipsychotic medications that have a propensity of causing detrimental metabolic side effects could have affected the results of our study. We did not exclude patients with pre-existing metabolic abnormalities or metabolic syndrome before advent of mECT. Furthermore, lack of control group and absence of data for maintenance treatment warrants future studies of larger sample sizes to evaluate the dynamics of metabolic parameters in patients receiving mECT.

CONCLUSION

Our findings reveal that the prevalence of metabolic syndrome and metabolic abnormalities in patients receiving mECT is alarming, irrespective of their psychiatric diagnosis. This highlights the critical need of screening for metabolic syndrome as well as metabolic abnormalities, especially in older patients and those who have longstanding history of receiving mECT sessions. Metabolic screening and management should be conducted at an early stage, so as to employ timely medical care and to reduce the deadly sequalae of metabolic syndrome such as cardiovascular disease and premature death.

Authors contribution

A.K. conceptualized the study and wrote manuscript; R.R. performed data collection; I.H. performed statistical analysis; Z.A.W. and R.R. performed manuscript review and editing. All authors read and approved final version of the manuscript.

Abbreviations

mECT: Modified Electroconvulsive therapy

NCEP ATP-III: National Cholesterol Education Program Adult Treatment Panel III

ASCVD: Atherosclerotic cardiovascular disease

MetS: Metabolic syndrome

TSH: Thyroid-stimulating hormone

HDL: High density lipoprotein

BP: Blood pressure

Ethics approval and consent to participate

The study was accorded approval from Institutional Review Board of Government Medical College, Srinagar, India, with reference number: IRBGMC/PSY365, dated: 29/11/2023.

Written informed consent was taken from all the participants and guardians. This study was carried out in accordance with the principles as enunciated in the Declaration of Helsinki.

Data availability statement

Data will be made available on reasonable request.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.