Search results

The search strategy identified 1030 articles, of which 19 were excluded as not being in English and 65 were duplicates. A total of 946 abstracts were further screened, and 83 articles retrieved. As noted in the PRISMA flowchart, 38 studies were further excluded as they had non-psychiatric patients and 16 studies included younger patients. There were seven reviews, three conference abstracts and eight case reports that did not meet our inclusion criteria. Two studies were not included as, despite all attempts, it was not possible to retrieve them from the searches. Only nine studies met all the criteria and were included in the review. More details of these studies are provided in the tables. Nine studies were initially identified.^{Reference Van Zyl, Wieczorek and Reilly5,Reference Ellis, Grubb, Mustoe, Watkins, Codling and Fitch20–Reference Schmedt and Garbe27} Four other studies were identified through cross-referencing articles.^{Reference Yoshizawa, Takeshima, Ishino, Ogasawara, Fujiwara and Itoh6,Reference Wang, Yang, He, Jiang, Gao and Liu12,Reference Liu, O'Rourke and Van Nguyen28,Reference Gaertner, Piémont, Faller, Bertschy, Hallouche and Mirea29} In total, we identified 13 studies that met our criteria.

Ten studies included patients from psychiatric in-patient units (summarised in Table 1), and three studies included patients from geriatric (physical health/acute care) units with psychiatric diagnoses (summarised in Table 2). Two studies were prospective in design,^{Reference Delluc, Montavon, Canceil, Carpentier, Nowak and Mercier21,Reference Weill-Engerer, Meaume, Lahlou, Piette, Saint-Jean and Sachet26} and the rest were retrospective in nature, with cross-sectional assessment of patient records. Two studies were part of local trust audits to assess factors associated with VTE in older in-patients.^{Reference Van Zyl, Wieczorek and Reilly5,Reference Ellis, Grubb, Mustoe, Watkins, Codling and Fitch20} The ten studies from psychiatric units included a total sample size of 101 458 in comparison with 5780 identified from geriatric settings. Schmedt and Garbe^{Reference Schmedt and Garbe27} had the highest sample size of 72 591, followed by Wang et al^{Reference Wang, Yang, He, Jiang, Gao and Liu12} with 12 939, Gaertner et al^{Reference Gaertner, Piémont, Faller, Bertschy, Hallouche and Mirea29} with 6218 and Ishida et al^{Reference Ishida, Shibahashi, Sugai, Abe, Hamabe and Kashiyama22} with 5268. Other studies had lower sample sizes.

Table 1 Study characteristics of psychiatric in-patients

VTE, venous thromboembolism; HRSD, Hamilton Rating Scale for Depression; HRSA, Hamilton Rating Scale for Anxiety; CE CT, contrast-enhanced computerised tomography.

Table 2 Study characteristics, geriatric settings

VTE, venous thromboembolism; 5HT, 5Hydroxy tryptophan.

We performed a quality assessment of the included studies, using the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.^{Reference Downes, Brennan, Williams and Dean19} Because of the heterogeneity of the studies included and two studies being retrospective in nature, only 11 studies could be qualitatively assessed. The quality assessment is summarised in Table 3. Because of the cross-sectional nature of the studies, most studies were limited in their quality, with only three studies being good.^{Reference Delluc, Montavon, Canceil, Carpentier, Nowak and Mercier21,Reference Kleijer, Heerdink, Egberts, Jansen and van Marum23,Reference Schmedt and Garbe27}

Table 3 National Institutes of Health quality assessment tool for observational cohort and cross-sectional studies

Rates of VTE

Ten studies provide occurrence rates of VTE in their populations. In psychiatric units, VTE rates ranged from 0.9 to 10.5%.^{Reference Wang, Yang, He, Jiang, Gao and Liu12,Reference Delluc, Montavon, Canceil, Carpentier, Nowak and Mercier21–Reference Kleijer, Heerdink, Egberts, Jansen and van Marum23,Reference Takeshima, Ishikawa, Shimizu, Kanbayashi and Shimizu25,Reference Liu, O'Rourke and Van Nguyen28,Reference Gaertner, Piémont, Faller, Bertschy, Hallouche and Mirea29} Delluc et al found the incidence of VTE was higher in patients older than 75 years, at 8.2%, compared with a rate of 3.5% across all age groups. Weil-Engerer et al found VTE incidence was higher in acute in-patient settings compared with long-term units.^{Reference Delluc, Montavon, Canceil, Carpentier, Nowak and Mercier21,Reference Weill-Engerer, Meaume, Lahlou, Piette, Saint-Jean and Sachet26} Yoshizawa et al found that 10.5% of patients with depression developed VTE, all of whom were asymptomatic.^{Reference Yoshizawa, Takeshima, Ishino, Ogasawara, Fujiwara and Itoh6} These high rates may be reflective of the authors screening all the patients for VTE, but may also possibly be a result of their stronger methodological approach. Table 4 shows comparison of sample sizes, VTE rates and risk factors between the studies from psychiatric and geriatric settings.

Table 4 Comparison between psychiatric and geriatric studies

VTE, venous thromboembolism.

Age

Increasing age is an important risk factor for the development of VTE. Around 80% of studies included in this review note that older patients were at higher risk of developing VTE, and this was across both psychiatric and geriatric in-patient units.^{Reference Wang, Yang, He, Jiang, Gao and Liu12,Reference Ellis, Grubb, Mustoe, Watkins, Codling and Fitch20–Reference Kleijer, Heerdink, Egberts, Jansen and van Marum23,Reference Weill-Engerer, Meaume, Lahlou, Piette, Saint-Jean and Sachet26} Weill-Engerer et al found the odds of VTE increased 1.5-fold over 10 years.^{Reference Weill-Engerer, Meaume, Lahlou, Piette, Saint-Jean and Sachet26} Some risk factors were age-related, as one study reported dementia as a risk factor for VTE only in patients older than 75 years of age.^{Reference Delluc, Montavon, Canceil, Carpentier, Nowak and Mercier21} Wang et al noted that patients at risk of VTE tended to be older if they were diagnosed as having psychosis.^{Reference Wang, Yang, He, Jiang, Gao and Liu12} Interestingly, one study reported no association between age and the risk of developing VTE.^{Reference Liu, O'Rourke and Van Nguyen28} This difference might have been because of its small sample size.

Gender

Results were mixed regarding the association between gender and risk of VTE. Thus, four studies noted that women were at higher risk of developing VTE.^{Reference Van Zyl, Wieczorek and Reilly5,Reference Wang, Yang, He, Jiang, Gao and Liu12,Reference Ishida, Shibahashi, Sugai, Abe, Hamabe and Kashiyama22,Reference Schmedt and Garbe27} Only one study reported higher rates of VTE in men (54%) compared with controls, but this result was not statistically significant.^{Reference Gaertner, Piémont, Faller, Bertschy, Hallouche and Mirea29} Four studies did not report a link between the gender of patients and their risk of VTE.^{Reference Yoshizawa, Takeshima, Ishino, Ogasawara, Fujiwara and Itoh6,Reference Delluc, Montavon, Canceil, Carpentier, Nowak and Mercier21,Reference Takeshima, Ishikawa, Shimizu, Kanbayashi and Shimizu25,Reference Liu, O'Rourke and Van Nguyen28}

Diagnosis

Psychiatric illness by itself is associated with higher risk of developing VTE. Rates of VTE occurrence differ based on psychiatric diagnosis. Wang et al noted the occurrence was highest in patients with organic mental illness (5.6%), followed by mood disorder (1.07%), schizophrenia (1.1%) and other mental health diseases, including neurotic disorder and substance-induced mental health disorders.^{Reference Wang, Yang, He, Jiang, Gao and Liu12} This was also reported by Delluc et al, who found that patients with dementia who were older than 75 years of age are were higher risk of developing VTE, with an incidence ranging from 8.2 to 12.5%.^{Reference Delluc, Montavon, Canceil, Carpentier, Nowak and Mercier21} Additionally, there was an association between dementia in patients on old-age wards and the risk of developing VTE.^{Reference Ellis, Grubb, Mustoe, Watkins, Codling and Fitch20} In contrast, Liu et al found that wandering behaviour in dementia was associated with reduced risk of VTE, with 0.1% of patients with dementia developing VTE compared with 5.8% of patients without dementia (P < 0.07).^{Reference Liu, O'Rourke and Van Nguyen28}

Depression was found to be associated with VTE in three studies.^{Reference Yoshizawa, Takeshima, Ishino, Ogasawara, Fujiwara and Itoh6,Reference Ishida, Shibahashi, Sugai, Abe, Hamabe and Kashiyama22,Reference Liu, O'Rourke and Van Nguyen28} Liu et al found patients with depression had higher risk of VTE compared with those without depression (6.3 v. 0.8%, P < 0.043).^{Reference Liu, O'Rourke and Van Nguyen28} One study reported that the severity of depression as rated by Hamilton Rating Scale for Depression (HRSD) score was associated with high risk of VTE, with an odds ratio of 1.22 (95% CI 1.08–1.3; P < 0.001).^{Reference Yoshizawa, Takeshima, Ishino, Ogasawara, Fujiwara and Itoh6} In keeping with this, Wang et al reported that higher HRSD scores were associated with VTE risk, whereas the Hamilton Rating Scale for Anxiety (HRSA) scores were found to be protective factors.^{Reference Wang, Yang, He, Jiang, Gao and Liu12}

Catatonia was associated with increased risk of developing VTE. VTE was observed in 61.1% (11/18) of patients with catatonia, 4.1% (11/270) of restrained patients without catatonia and 1.2% (17/1393) of unrestrained patients without catatonia.^{Reference Takeshima, Ishikawa, Shimizu, Kanbayashi and Shimizu25} This finding was replicated by Ishida et al, who also reported an association between catatonia and VTE, with an odds ratio of 5.84 (95% CI 2.69–12.70; P < 0.001).^{Reference Ishida, Shibahashi, Sugai, Abe, Hamabe and Kashiyama22} The remaining studies either did not record or did not identify any significant association between other mental illness and the risk of VTE.^{Reference Kleijer, Heerdink, Egberts, Jansen and van Marum23,Reference Gaertner, Piémont, Faller, Bertschy, Hallouche and Mirea29}

Medication

The association between medication use and DVT reported mixed findings. In terms of antipsychotic use, most studies found no association between the use of antipsychotics and VTE.^{Reference Wang, Yang, He, Jiang, Gao and Liu12,Reference Ellis, Grubb, Mustoe, Watkins, Codling and Fitch20,Reference Ishida, Shibahashi, Sugai, Abe, Hamabe and Kashiyama22,Reference Kleijer, Heerdink, Egberts, Jansen and van Marum23,Reference Takeshima, Ishikawa, Shimizu, Kanbayashi and Shimizu25,Reference Liu, O'Rourke and Van Nguyen28,Reference Gaertner, Piémont, Faller, Bertschy, Hallouche and Mirea29} A nested case–control study of 111 818 patients with at least one antipsychotic drug prescription during 1998–2008 reported that current use of antipsychotics was not associated with the risk of VTE (odds ratio 0.9, 95% CI 0.7–1.1). The study found no difference between typical (chlorpromazine, chlorprothixene, periciazine, perphenazine, pipamperone) and atypical antipsychotics (risperidone, olanzapine, clozapine, quetiapine, aripiprazole, tiapride, sulpiride) in terms of risk of VTE.^{Reference Kleijer, Heerdink, Egberts, Jansen and van Marum23} In contrast, a large study found significantly increased risk of VTE for current antipsychotic use (odds ratio 1.23, 95% CI 1.01–1.50) and concurrent use of second- and first-generation drugs (odds ratio 1.62, 95% CI 1.15–2.27). They also note that the odds ratio was significantly elevated for patients who were newly prescribed antipsychotics within 90 days (odds ratio 1.63, 95% CI 1.10–2.40) of commencement of medication, but not for those who were already using antipsychotics (odds ratio 1.09, 95% CI 0.87–1.36).^{Reference Schmedt and Garbe27} Similarly, a case report of four patients who developed VTE while on risperidone noted an incidence rate of 5.2% in patients who received risperidone for a variety of psychiatric diagnoses.^{Reference Gallerani, Imberti, Mari, Marra and Manfredini24}

None of the studies included in this review found any association between the use of antidepressants and the risk of VTE.

Takeshima et al converted administered antidepressants in imipramine equivalents into three groups: 0 mg/day, >0 mg and <150/day, or >150 mg/day, and compared them with the risk of VTE, although they did not specify the antidepressants prescribed. Thirty-five patients had received at least one antidepressant, and they found no association between the dose of antidepressant and VTE.^{Reference Takeshima, Ishikawa, Shimizu, Kanbayashi and Shimizu25} With regards to use of other psychotropic medications, one study reported that the use of antidementia drugs was associated with the risk of VTE, both at day 10 and day 90 of admission, but found no association between the use of anxiolytics and sedatives and VTE. In this study, individual drugs and their doses were not specified.^{Reference Delluc, Montavon, Canceil, Carpentier, Nowak and Mercier21}

Mobility

Psychiatric patients can have immobility resulting from psychomotor retardation, catatonia, excess sedation or physical restraint. Three studies did not find any association between reduced physical mobility and the risk of VTE.^{Reference Wang, Yang, He, Jiang, Gao and Liu12,Reference Ellis, Grubb, Mustoe, Watkins, Codling and Fitch20,Reference Gaertner, Piémont, Faller, Bertschy, Hallouche and Mirea29} Weil-Engerer et al found that restriction of mobility (both the type and duration of immobility) was associated with patients developing VTE.^{Reference Weill-Engerer, Meaume, Lahlou, Piette, Saint-Jean and Sachet26} Additionally, Ishida et al noted that catatonia was associated with elevated risk of VTE in psychiatric in-patients.^{Reference Ishida, Shibahashi, Sugai, Abe, Hamabe and Kashiyama22} Takashima et al found that 61.1% (11/18) of patients with catatonia developed VTE, compared with only 4.1% (11/270) of restrained patients without catatonia and 1.2% (17/1393) of non-restrained patients without catatonia who developed VTE.^{Reference Takeshima, Ishikawa, Shimizu, Kanbayashi and Shimizu25}

Risk assessment

Studies included in this review employed different methods in the assessment of risk factors for VTE. One local audit^{Reference Ellis, Grubb, Mustoe, Watkins, Codling and Fitch20} used the UK Department of Health VTE risk assessment tool. Liu et al^{Reference Liu, O'Rourke and Van Nguyen28} used a risk assessment tool previously developed by Malý et al.^{Reference Malý, Masopust, Hosák and Konupcíková30} Liu et al categorised patients into three groups (low, moderate and high, based on VTE scores); 81.8% (157/192) were assessed as low risk and 18.2% (35/192) as medium/high risk.^{Reference Liu, O'Rourke and Van Nguyen28} Ishida et al developed their own screening tool with risk factors specific to psychiatric patients. This included factors such as age, gender, depressive episode, catatonia, active cancer, previous VTE and transfer from a general hospital, giving a score ranging from 0 to 14. A cut-off value of 2 had a sensitivity of 0.927, a specificity of 0.535 and a negative predictive value of 0.993. They reported that their tool was able to discriminate between patients with moderate to higher risk.^{Reference Ishida, Shibahashi, Sugai, Abe, Hamabe and Kashiyama22} Overall rates of screening and assessment for VTE were quite variable (5.9.24). Ellis et al reported that despite 30.6% of their sample being identified as at risk of VTE, only 4.3% had undergone risk assessment.^{Reference Ellis, Grubb, Mustoe, Watkins, Codling and Fitch20} This was even lower in an audit, where none of the patients underwent risk assessment at admission.^{Reference Van Zyl, Wieczorek and Reilly5}

Prophylaxis

Most of the studies in this review either did not report use of thromboprophylaxis or the rates were low. In Delluc et al, only 0.4% of patients received prophylactic anticoagulation on the ward, whereas an audit found that none of their patients received any prophylactic measures.^{Reference Van Zyl, Wieczorek and Reilly5,Reference Delluc, Montavon, Canceil, Carpentier, Nowak and Mercier21} The highest rates were noted in a cross-sectional study, where 16.7% (32/192) received VTE prophylaxis. This included thromboembolic deterrent (thrombo–embolus deterrent hose stockings alone, unfractionated heparin/low-molecular-weight heparin, or thrombo–embolus deterrent stockings combined with unfractionated heparin/low-molecular-weight heparin).^{Reference Liu, O'Rourke and Van Nguyen28}

An audit in the UK recorded the reasons for not prescribing VTE prophylaxis for their patients. There were potential contraindications or concerns about prescribing VTE prophylaxis in 14.9% of patients. These included factors such as active self-harm, high risk of self- harm/previous self-harm and self-neglect, among others.^{Reference Ellis, Grubb, Mustoe, Watkins, Codling and Fitch20}