Psychological controversies in gastroparesis: A systematic review

Table 1 Summary of papers reviewed

Ref.	Study characteristics	Participant details	Psychological measures used	Relevant findings	Conclusion
Soykan et al[6]	Cohort study using six-years of hospital records. Demographic and clinical data evaluated at entry to the hospital and most recent follow-up	n = 146 (120 females, 26 males). Mean age: 45.0 yr. Etiology: 42 DG, 52 IG, 19 post-surgical, 11 Parkinson’s disease, 7 collagen vascular disorders, 6 intestinal pseudo-obstruction, 9 other	CES-D, SCL-90	23% of IG patients were thought to be depressed, and 50% displayed significant elevations on gastrointestinal psychosomatic susceptibility	Psychological status may be predictive of response to prokinetic therapy
Harrell et al[31]	Cross-sectional study with an interview, patients classified into a clinical subgroup based on predominant symptoms	n = 100 (87 females, 13 males). Mean age: 48.0 yr. Etiology: unspecified	SF-12	QoL (subscales and mental/physical component summaries) was significantly diminished in all gastroparesis patients when compared to population norms, but did not differ between groups based on predominant gastroparesis symptoms. QoL negatively correlated with physical symptom scores	Predominant-symptom classification may be useful in the management of gastroparesis
Bielefeldt et al[8]	Cross-sectional study with a qualitative interview	n = 55 (44 females, 11 males). Mean age: 42.4 yr. Etiology: 11 DG, 29 IG, 8 connective tissue disease, 4 post-surgery or trauma, 1 osteogenesis imperfect, 1 mitochondrial myopathy, 1 Marfan syndrome	HADS, SF-12, open-ended interview questions	Patients had moderately elevated scores for anxiety and depression, 74% met screening criteria for anxiety or depression, 29% were above the threshold for clinically relevant affective spectrum disorders, and eighteen patients were receiving chronic anti-depressant medication. Patients demonstrated impaired QoL compared to population norm, with no differences between etiologies. Physical symptoms were inversely related to the physical component score on SF-12. Symptom severity was positively correlated with depression scores, but not anxiety, symptom duration or degree of gastric delay. Qualitative data: patients were asked to describe the impact of gastroparesis on their lives and three main topics were identified: 1) eating out/social functions, 2) fatigue, 3) strain on relationships. Nausea and vomiting were the most troublesome symptoms, and patients also reported a fear of unrelenting disease, as well as frustration/dissatisfaction with healthcare providers	Gastroparesis treatment must focus on improving QoL. The results of this study provide support for the use of psychologically based interventions in gastroparesis
Jung et al[14]	Cohort study using medical records	Definite gastroparesis = 83 (68 female, 15 males). Mean age at onset: 44.0 yr. Etiology: 21 DG, 41 IG, connective tissue disease 9, hypothyroidism 1, malignancy 2, abdominal surgery 6, provocation drugs 19, end-stage renal disease 4	None reported. Evidence obtained from medical records.	Of 83 patients with definite gastroparesis, 25 had evidence of comorbid psychiatric illness in their medical records. Twenty patients had "anxiety/depression" and five had "other"	Gastroparesis is difficult to manage and represents a major disease burden
Hasler et al[7]	Cross-sectional study. Data obtained from the Gastroparesis Registry	n = 299 (245 females, 54 males). Mean age: 43.0 yr. Etiology: 100 DG, 199 IG	BDI, STAI	Depression and anxiety scores increased with greater physician-rated, and patient-rated, symptom severity. Nausea and vomiting were greater in patients with more severe depressive symptoms. Bloating and postprandial fullness were greater in patients with more severe depressive symptoms, state and trait anxiety. Higher depression scores were associated with prokinetic or antiemetic drug use, and increased hospitalizations. Higher state anxiety was associated with anxiolytic use, while higher trait anxiety was associated with antidepressant use and increased hospitalizations. Depression and anxiety scores did not differ across etiology or degree of gastric retention. Higher symptom severity score was predictive of higher depression and state anxiety score. Use of anxiolytics was predictive of state anxiety, use of anti-depressants was predictive of greater trait anxiety score, and male gender was predictive of higher state anxiety	The physical and psychological features of gastroparesis both need to be considered in the development of individualized patient treatment plans. Longitudinal studies must be conducted to evaluate the relationship between psychology and gastroparesis, and whether psychological treatment can affect the physical symptoms of gastroparesis
Cherian et al[10]	Cross-sectional study	n = 68 (58 females, 10 males). Mean age: 42.6 yr. Etiology: 18 DG, 50 IG. 52 Functional Dyspepsia patients also studied	PAGI-QOL	DG patients scored significantly higher than IG patients on the following PAGI-QOL subscales: diet, daily activities, relationships. When pain severity was correlated with QOL subscales, there was a moderate correlation with avoiding physical activity, taking longer to perform daily activities, worry about having stomach problems in public, and depending on others to perform activities	Abdominal pain is an important symptom of gastroparesis and is associated with decreased QoL
Hasler et al[32]	Cross-sectional study. Data obtained from the Gastroparesis Registry	n = 243 (214 females, 29 males). Mean age: 41.0 yr. Etiology: 116 DG, 219 IG	PAGI-QOL, SF-36	Patients had moderately impaired QoL, with inverse correlation to bloating severity	Bloating is a prevalent symptom in gastroparesis and is associated with impaired physical and mental QoL
Parkman et al[12]	Cross-sectional study. Data obtained from the Gastroparesis Registry	n = 243 (214 females, 29 males). Mean age: 41.0 yr. Etiology: 243 IG	BDI, STAI	36% of participants demonstrated severe state anxiety, 35% demonstrated severe trait anxiety, and 18% demonstrated severe depression. Overweight IG patients were more likely to have an anxiety disorder. Major depressive disorder was associated with greater symptom severity. Anxiety and depression scores tended to be higher in patients with more severely delayed gastric emptying	Symptoms, gastric retention, current treatment, and psychosocial factors all play a role in the severity of IG
Jaffe et al[33]	Cross-sectional study	n = 59 (52 females, 7 males). Mean age: 43.0 yr. Etiology: 20 DG, 39 IG	PAGI-QOL, SF-36	Nausea/vomiting subscale of PAGI-SYM correlated with lower scores on the PAGI-QOL. SF-36 scores were significantly decreased in gastroparesis patients compared to population norms	Nausea is a predominant symptom of gastroparesis that is associated with impaired QoL
Cherian et al[2]	Cross-sectional study	n = 156 (126 females, 30 males). Mean age: 41.1 yr. Etiology: 42 DG, 114 IG. 52 FD patients also studied	HADS, PAGI-QOL	Increased fatigue was associated with decreased QoL, increased depression, and decreased anxiety. All but one patient met criteria for depression, and the same was found for anxiety	Fatigue is a significant symptom in gastroparesis and is associated with decreased QoL. Psychiatric interventions may help in fatigue management
Hasler et al[29]	Cross-sectional study. Data obtained from the Gastroparesis Registry	n = 393 (327 females, 66 males). Mean age: 42.9 yr. Etiology: 137 DG, 256, IG	BDI, STAI, PAGI-QOL, SF-36	Depression and anxiety were higher in those with greater symptom severity. Impaired PAGI- QOL and SF–36 physical component scores related to increased pain and/or discomfort severity	The influence of predominant pain/discomfort on disease severity is at least as great as predominant nausea/vomiting
Friedenberg et al[30]	Cross-sectional study	n = 255 (212 females, 43 males). Mean age: 42.0 yr. Etiology: 180 IG, 64 DG, 4 post-surgical, 7 other	PAGI-QOL	African American and Hispanic patients had lower scores on clothing and psychological PAGI-QOL subscales than Caucasian patients resulting in lower QoL overall. PAGI-SYM and PAGI-QOL had a negative correlation and 30% of the variation in QoL could be explained by symptom severity	Future population-based studies into the influence of race on symptoms and QoL in gastroparesis are warranted
Liu et al[36]	Randomized controlled trial with follow-up at 3, 7, 10, and 17 d post intervention	n = 120 (70 females, 50 males). Mean age: 60.5 yr. Etiology: 120 post-surgical	CES-D	A group that underwent a mental intervention had faster recovery from post-surgical gastroparesis (e.g., extubation time, eating recovery) compared to a control group. Depression was comparable in groups at baseline, but mental intervention group had lower scores than control at 3, 7, 10, and 17 d post-intervention	Mental intervention is important in post-surgical recovery, and primary nurses should be trained to care for patients physically and psychologically post-surgery
Pasricha et al[26]	Cross-sectional study. Data obtained from the Gastroparesis Registry	n = 262 (215 females, 47 males). Mean age: 44.0 yr. Etiology: 177 IG, 85 DG	PAGI-QOL, BDI, STAI	Mild improvement in QoL from baseline to follow-up at 48 weeks (PAGI-QOL and SF-36 physical and mental component scores), with no significant difference in QoL improvement across etiologies. No significant changes in depression or anxiety levels over the 48-week follow-up period. Moderate to severe depression and the use of anxiolytics at baseline were negative predictors of symptomatic improvement at follow-up, while anti-depressant use was a positive predictor	Less than a third of patients with gastroparesis experience symptomatic improvement over time and QoL remains impaired. Depression is an important predictor of symptomatic improvement
Cutts et al[34]	Cross-sectional study	n = 235 (186 females, 49 males). Mean age: 47.0 yr. Etiology: 125 IG, 68 DG, 28 post-surgical, 14 unspecified	SF-36	Reports correlations between SF-36 subscales and gastroparesis symptoms. Negative correlations with Physical Function subscale: bloating severity, bloating frequency, epigastric pain severity. Negative correlations with Bodily Pain subscale: bloating severity, bloating frequency, epigastric pain severity, epigastric pain frequency, epigastric burn frequency. Negative correlations with Social Functioning subscale: epigastric pain frequency, vomiting severity. Negative correlations with Role Emotional subscale: bloating severity, bloating frequency. Negative correlation with mental health subscale: bloating severity. The only positive correlation was between the Role Emotional subscale and epigastric pain severity	Generic and global QoL tools may not accurately reflect the experience of gastroparesis patients
Lacy et al[35]	Cross-sectional study	n = 250 (196 females, 54 males). Mean age: 46.8 yr. Etiology: 126 IG, 37 DG, 34 post-viral, 17 post-surgical, 11 connective tissue disorder, 10 neurologic, 5 post-vaccination, 3 hollow visceral myopathy, 3 vascular, 4 miscellaneous	SF-36	IG patients had higher physical functioning, mental health, and role-physical scores compared to DG patients. Patients with DG had lower physical component summary scores than patients with IG or other etiologies. Patients with IG had higher mental component summary scores than patients with DG or other etiologies	It is important that gastroparesis interventions aim to lessen pain and improve QoL in patients

DG: Diabetic gastroparesis; IG: Idiopathic gastroparesis; QoL: Quality of life.

Table 2 Summary of participant characteristics

	n
Number of studies included in this review	16
Number of participants identified in the studies	2967
Disease etiology
Unspecified	118
Idiopathic	1850
Diabetic	761
Post-surgical	198
Other (e.g., connective tissue disorder, Parkinson’s disease)	151
Gender
Female	2434
Male	533
Mean age	44.6

Table 3 General recommendations and questions for future research

General recommendations:

Identify prevalence of psychological conditions based upon standardized and validated assessment tools (e.g., SCID[37], MINI[38])

Use standardized assessment of gastroparesis (e.g., gastric emptying scintigraphy, PAGI-SYM[39])

Use validated psychological scales to assess, anxiety, depression, stress (e.g., BDI[40], BAI[41], STAI[42], DASS[43]) and QoL measures relevant to individuals with upper gastrointestinal disorders (e.g., PAGI-QoL[44])

Use and provide clear scoring information

Report assessment results in a manner that allows comparison across studies (e.g., standardized cut-off scores)

Psychological interventions:

Randomized control trial design

Prior to intervention, power analyses conducted

Clear details of intervention content made fully available to allow other researchers to review and undertake accurate replication

Gastroparesis-focused interventions

Include measures that assess a cost/benefit analysis, engagement of medical services

Where possible, patients, assessors, and statistician blinded

Independent evaluation of intervention session recordings to ensure protocol/treatment consistency

Psychological interventions need to be clearly identified and undertaken by trained and appropriately qualified individuals (i.e., psychologists, psychiatrists)

Identify clear inclusion and exclusion criteria

Identifying if (and where possible control for) participants have/have not received or are currently receiving psychotherapy (including type, duration etc.), using psychotropic medication, are on specialized diets for their gastroparesis

Utilize valid measures which can be accurately compared to other intervention studies

Evaluate participant engagement in therapy (e.g., % attendance to sessions, completion of homework)

Evaluate differences between completers versus non-completers

Include long-term post-therapy efficacy review time points (i.e., 1 and 2 yr post-intervention)

Future research questions:

What is the prevalence of psychopathology in gastroparesis compared to other gastroenterological cohorts?

What psychological processes act as moderating/mediating factors between gastroparesis symptom activity and outcome variables such as QoL, anxiety, and depression (e.g., personality, coping style, self-efficacy)?

How may gender impact upon the presentation and course of gastroparesis and associated psychological distress?

How may historical and current stressors and/or traumas impact upon the presentation and course of gastroparesis?

To what extent does duration of symptoms/disease influence the relationship between gastroparesis and psychological distress?

QoL: Quality of life.