Main findings

We found 61 comparative analyses relating to the prescription of 12 classes of medication including lipid-regulating agents (includes statins), beta-blockers, antiplatelet and anticoagulant drugs, ACE/ARBs, insulin, cytotoxic chemotherapy, anti-inflammatories, HRT for osteoporosis and HAART for HIV. Patients with severe mental illness had an odds ratio of 0.74 (95% CI 0.63–0.86) for a comparable medication prescription. The differences were found largely in drugs for cardiovascular indications. For example, patients with severe mental illness received lower than expected prescriptions for ACE/ARBs, beta-blockers and statins. Combining all types of mental illness and all classes of drug suggested that patients with any type of mental illness had an odds ratio of 0.78 (95% CI 0.73–0.84, P = 0.0001) of comparable medication (data not shown). Given a typical control event rate (i.e. receipt of medication in the comparison group) of 70%, the actual rate of undertreatment can be estimated at 8% (95% CI 5–12) in those with other mental illness, 10% in those with severe mental illness and 12% in schizophrenia, a disparity that could be classified as ‘inequitable’ or ‘suboptimal’ receipt of medication according to our a priori definition.

Limitations

Several limitations should be acknowledged. First, we had no a priori protocol for this study but attempted to follow the review strategy suggested in the PRISMA standard. Heterogeneity was found in 5 out of 11 main analyses (Table 1) and this had the effect of rendering the odds ratios observed for affective disorders non-significant. We used the Newcastle-Ottawa scale, which is only one of several possible methods. ^{Reference Stang61} In two studies involving HAART there was no adjustment made for demographic, illness or prescribing variables ^{Reference Mijch, Burgess, Judd, Grech, Komiti and Hoy51,Reference Yun, Maravi, Kobayashi, Barton and Davidson60} (see Table DS1) and therefore these data should be interpreted with caution. Without adjustment it is possible that the group with mental illness had more severe physical illness than the comparison group – although this should of course favour higher rates of prescribing, not lower rates. One study reported hazard ratios with no control event rate, ^{Reference Himelhoch, Moore, Treisman and Gebo46} therefore we estimated the control event rate using data from related publications from the same group (pending confirmation from the authors). Another limitation is that the definition of mental illness, particularly severe mental illness varied considerably between studies, with seven studies defining mental illness using routine clinical interviews and one using prescription of haloperidol as a marker of mental ill health. The remaining studies used ICD-9 coding. A further important limitation is that most studies specified only that the mental health diagnosis was present in the year preceding the prescription of medication and therefore concurrent mental illness, symptoms of mental illness and severity of mental illness cannot be adequately reported. We also note that although the majority of disparities were manifest in drugs prescribed for cardiovascular conditions, the sample size was modest for most other medical conditions. We also note that in all but 1 of the 23 studies the setting was a country where health insurance is operating (largely USA), as opposed to socialised healthcare. Further studies should examine potential prescribing inequalities in countries with nationalised healthcare. Finally, and perhaps most importantly, all but two studies (see overleaf) measured prescribing from electronic databases based on naturalistic observational data and thus no information was available on patient v. prescriber influences on low receipt of necessary medication.

FIG. 2 Prescribing differences for severe mental illness v. no mental illness: summary meta-analysis plot (random effects).

ACE, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; HAART, highly active antiretroviral therapy; HRT, hormone replacement therapy; IHD, ischaemic heart disease.

FIG. 3 Prescribing differences for affective disorder v. no mental illness: summary meta-analysis plot (random effects).

ACE, angiotensin-converting enzyme inhibitor; HAART, highly active antiretroviral therapy.

FIG. 4 Prescribing differences for other mental illness^a v. no mental illness: summary meta-analysis plot (fixed effects).

ACE, angiotensin-converting enzyme inhibitor; HAART, highly active antiretroviral therapy.

a. Other mental illness includes any type of mental ill health other than pure affective disorder, severe mental illness or schizophrenia.

Possible explanations for suboptimal prescribing

It is already widely known that people with mental ill health have problems with psychotropic medication adherence. ^{Reference Mitchell62,Reference Mitchell and Selmes63} This also applies to adherence to physical health medications. ^{Reference DiMatteo, Lepper and Croghan64–Reference Katon, Russo, Lin, Heckbert, Karter and Williams66} However, the studies reviewed here measure medication prescribing according to notations in medication databases (with the exception of Bishop et al who used notations in medical notes ^{Reference Bishop, Alexander, Lund and Klepser39} and Suvisaari et al who used patient-reported medication at interview ^{Reference Suvisaari, Jonna Perälä, Saarni, Kattainen, Lönnqvist and Reunanen56} ). Thus, uptake of medication and adherence to medication was not measured. We suggest therefore that the amount of medication actually taken as directed was probably less than that recorded here, and actual disparities in medication consumption may be more severe than disparities in prescribing. That said, some studies have found no difference or higher medication adherence to psychotropic drugs compared with physical health medication. ^{Reference Piette, Heisler, Ganoczy, McCarthy and Valenstein67,Reference Himelhoch, Brown, Walkup, Chander, Korthius and Afful68} It may be important to acknowledge that insurance coverage influences uptake of medication in the USA and Canada. ^{Reference Mulvale and Hurley69} However, the studies here do not measure uptake but rather prescribing. As many people with mental illness are unaware of their formal medical diagnosis and uninformed about their physical health medication, ^{Reference Suvisaari, Jonna Perälä, Saarni, Kattainen, Lönnqvist and Reunanen56} we suggestthatthe disparitiesnoted are more likely to relate to physician habits than patient preferences.

TABLE 1 Overview of meta-analytic resultsFootnote ^a

	Severe mental illness/schizophrenia				Affective disorder				Other mental illnessFootnote b
	OR (95% CI)	Z	P	I 2, % (95% CI)	OR (95% CI)	Z	P	I 2, % (95% CI)	OR (95% CI)	Z	P	I 2, % (95% CI)
All classes	0.74 (0.63–0.86)	–3.83	0.001	97.2 (96.9–97.5)	0.75 (0.55–1.02)	–1.82	0.07	94.6 (92.9–95.8)	0.95 (0.92–0.98)	–3.07	0.002	64.5 (21.4–79.3)
ACEs or ARBs	0.89 (0.81–0.98)	–2.31	0.021	74 (18.6–86.8)	Insufficient data				0.92 (0.85–0.99)Footnote c	–2.27	0.02	0 (0–72.9)
Anticoagulant (including aspirin)	0.99 (0.96–1.03)	–0.67	0.500	3.4 (0–57.8)	Insufficient data				Insufficient data
Beta-blockers	0.90 (0.84–0.96)	–3.2	0.001	63.1 (0–81.8)	0.76 (0.45–1.29)	–1.01	0.3134	93.5 (83.7–96.3)	Insufficient data
Anticholesterol drugs	0.59 (0.33–1.06)	–1.75	0.08Footnote d	98.7 (98.4–98.9)	0.92 (0.64–1.32)	–0.46	0.6469	77.2 (0–89.7)	Insufficient data
HIV HAART medication	Insufficient data				Insufficient data				0.98 (0.75–1.28)	–0.164	0.8693	82.6 (36–91.5)

ACEs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; HAART, highly active antiretroviral therapy.

a. Analysis: Z-test: test that odds ratio differs from 1; I ², inconsistency: <80% equals low >80% equals high.

b. Other mental illness includes any type of mental ill health other than pure affective disorder, severe mental illness or schizophrenia.

c. Fixed-effects odds ratio.

d. Significant for statins alone.

Where physical health medication is prescribed by mental health professionals several factors may influence underprescribing. Previous work has shown that mental health professionals often miss physical conditions in their patients ^{Reference Koranyi26,Reference Felker, Yazell and Short70,Reference Koran, Sox, Marton, Moltzen, Sox and Kraemer71} and undertake physical examinations in less than 50% of their patients. ^{Reference Bobes, Alegría, Saiz-Gonzalez, Barber, Pérez and Saiz-Ruiz72} Mental health professionals often do not feel confident in prescribing physical health medication. Yet in the majority of cases physical health medication is prescribed by physicians in primary care, internal medicine and related medical specialties. We already know that mental health status and prescription of antipsychotics reduces likelihood of medical monitoring (such as glycated haemoglobin (HBA1c) testing). ^{Reference Mitchell, Malone and Carney Doebbeling6,Reference Banta, Morrato, Lee and Haviland73} Primary care physicians often consider such patients to be ‘difficult to manage’, although many primary care physicians are willing to help with physical healthcare. ^{Reference Lester, Tritter and Sorohan74,Reference Oud, Schuling, Slooff, Groenier, Dekker and Meyboom-de Jong75} Where primary care physicians lack expertise in mental health they are less likely to offer general care to those with mental illness. ^{Reference Fleury, Bamvita and Tremblay76} Similarly when people with mental illness attend emergency departments they are less likely to be offered hospital care than other people. ^{Reference Sullivan, Han, Moore and Kotrla77} In general practice, cardiovascular risk factors are often recorded in the medical records for adults with long-term mental illness, but primary care physicians appear reluctant to intervene. ^{Reference Kendrick78} Clinician factors such as willingness to investigate, ability and enthusiasm to treat and willingness to offer follow-up are important predictors of quality of care. Because of medical and psychiatric comorbidity, seemingly unrelated conditions compete for clinicians’ attention. ^{Reference Piette and Kerr79} Against this, studies suggest that the adequacy of medical care may not be adversely influenced by the number of comorbid medical disorders. ^{Reference Min, Wenger, Fung, Chang, Ganz and Higashi80,Reference Higashi, Wenger, Adams, Fung, Roland and McGlynn81} Indeed, some have found that comorbidity favours superior care by virtue of higher than average healthcare visits. ^{Reference Kurdyak and Gnam82} Indirect evidence suggests that clinicians’ attitudes towards patients directly influence health outcomes. In one study in primary care, poor mental health status was linked with poor accessibility, poorer general practitioner attitude and less time spent with the general practitioner. ^{Reference Al-Mandhari, Hassan and Haran83} In a study of 59 patients seen in a US community mental health centre, 14% reported that they used the medical emergency department for their routine medical care needs and 45% said that their mental health provider did not ask them about medical issues. ^{Reference Levinson Miller, Druss, Dombrowski and Rosenheck84}

Three mitigating factors might explain low physician prescribing of physical health medication namely cautious prescribing, deferred prescribing and low patient acceptance of suggested medication. Regarding intentionally cautious prescribing, physicians’ prescription of cardiovascular medication may be cautious in light of possible links with suicide. ^{Reference Reith and Edmonds85} Most plausibly this could apply to cholesterol-lowering agents, ^{Reference Muldoon, Manuck, Mendelsohn, Kaplan and Belle86,Reference Lester87} beta-blockers ^{Reference Sorensen, Mellemkjaer and Olsen88} and angiotensin-receptor antagonists. ^{Reference Callréus, Agerskov Andersen, Hallas and Andersen89} Less likely but theoretically possible, physicians might be cautious about using aspirin together with selective serotonin reuptake inhibitors due to gastrointestinal bleeding, and ACE inhibitors and beta-blockers in people with mental illness who smoke. A second possibility is that treatment in some circumstances is deferred rather than omitted, although evidence suggests that in the context of mental illness most deferred treatment is not received at a later date. ^{Reference Evon, Verma, Dougherty, Batey, Russo and Zacks90} A third hypothesis underlying inadequate prescriptions is low uptake of care on account of patient preference. It is not yet clear if this is the primary explanation. ^{Reference Cradock-O'Leary, Young, Yano, Wang and Lee91–Reference Folsom, McCahill, Bartels, Lindamer, Ganiats and Jeste93} For example, Salsberry and colleagues (2005) found that compared with the general population, those with severe mental illness had more emergency department visits and visited a doctor more frequently, but despite this high healthcare utilisation had very low rates of cervical smears and mammograms. ^{Reference Salsberry, Chipps and Kennedy94} People with mental ill health perceive barriers to accessing primary physical healthcare. ^{Reference Levinson Miller, Druss, Dombrowski and Rosenheck84,Reference Dickerson, McNary, Brown, Kreyenbuhl, Goldberg and Dixon92,Reference Crews, Batal, Elasy, Casper and Mehler95–Reference Bradford, Kim, Braxton, Marx, Butterfield and Elbogen97} Patients often cite lack of availability of medical advice and poor quality of medical advice as influential. ^{Reference Levinson Miller, Druss, Dombrowski and Rosenheck84,Reference Druss and Rosenheck98,Reference O'Day, Killeen, Sutton and Iezzoni99} Observational evidence shows many have difficulty getting timely access to appropriate primary healthcare. ^{Reference Farmer27,Reference Bradford, Kim, Braxton, Marx, Butterfield and Elbogen97,Reference Rice and Duncan100,Reference Chwastiak, Rosenheck and Kazis101} For example, data from the 1999 Large Health Survey of Veterans found that veterans with schizophrenia, bipolar disorder or a drug use disorder were less likely to have had any primary care visit than those without these diagnoses, even after controlling for medical comorbidity. ^{Reference Chwastiak, Rosenheck and Kazis101}

Intervention to improve therapeutic care

Assuming these disparities in prescribing are robust, what can be done to improve quality of medical care? Druss & von Esenwein (2006) ^{Reference Druss and von Esenwein102} reviewed six randomised trials designed to improve medical care in psychiatric conditions. These studies demonstrated a substantial positive impact on linkage to and quality of medical care albeit with a diverse range of interventions. One study showed that a simple intervention could improve readiness to begin HAART. ^{Reference Balfour, Kowal, Silverman, Tasca, Angel and Macpherson103} Ismail et al and Winkley et al pooled 46 trials regarding the effect of psychological treatment on glycaemic control but showed only very modest effects in adults. ^{Reference Ismail, Winkley and Rabe-Hesketh104,Reference Winkley, Landau, Eisler and Ismail105} Anderson et al (1998) reported a meta-analysis of 43 studies involving strategies to improve the delivery of preventive care that could hold valuable lessons. ^{Reference Anderson, Janes and Jenkins106} In general, interventions were moderately effective in improving immunisation, screening and counselling. ^{Reference Anderson, Janes and Jenkins106} In this data-set, two studies examined the effect of antidepressant treatment on HAART utilisation in patients with depression. Tegger et al (2008) found that untreated patients were 40% as likely to receive HAART; in treated patients there was no significant difference. ^{Reference Tegger, Crane, Tapia, Uldall, Holte and Kitahata57} Similarly, Cook et al found that mental health treatment increased the probability of self-reported HAART use. ^{Reference Cook, Grey, Burke-Miller, Cohen and Anastos32} Primary care physician recommendation of screening has been shown to be one of the strongest predictors of receipts of screening. ^{Reference Friedman, Neff, Webb and Latham107–Reference Friedman, Puryear, Moore and Green110} Better communication between primary care providers and specialist mental health services might improve prescribing for mental and physical ill health. ^{Reference Oud, Schuling, Slooff, Groenier, Dekker and Meyboom-de Jong75,Reference Phelan, Stradins and Morrison111} However, in a trial of an integrated model of care for older people, the intervention helped with access but did not produce any significant treatment effects for depression or anxiety. ^{Reference Arean, Ayalon, Jin, McCulloch, Linkins and Chen112}

From a research perspective, a detailed examination of patient and provider influences on received medication is urgently needed. Clinically, we suggest that treatment of comorbid physical conditions is prioritised in patients with mental health concerns and closely monitored. ^{Reference Dickinson, Dickinson, Rost, DeGruy, Emsermann and Froshaug113} Clinicians caring for patients with physical and mental illness should take particular care to ensure optimal treatment is maintained in both areas. At an organisation level, monitoring systems are needed to ensure that the medical care of people with mental ill health is not overlooked.