The effect of Clinical Practice Guidelines on prescribing practice in mental health: A systematic review

Psychiatry Research xxx (xxxx) xxxx

Contents lists available at ScienceDirect

Psychiatry Research journal homepage: www.elsevier.com/locate/psychres

Review article

The effect of Clinical Practice Guidelines on prescribing practice in mental health: A systematic review Tony Nguyena,b, Natalie Seilera,b, Ellie Browna,b, Brian O'Donoghuea,b,c,

⁎

a

Orygen, The National Centre of Excellence in Youth Mental Health, 35 Poplar Road Parkville, Victoria 3052, Australia Centre for Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria 3052, Australia c Orygen Youth Health, 35 Poplar Road, Parkville, Victoria 3052, Australia b

ARTICLE INFO

ABSTRACT

Keywords: Practice guideline Practice guidelines as topic Practice patterns Physicians Evidence-based practice Mental health Psychotropic drugs

Clinical Practice Guidelines are succinct evidence-based recommendations and in psychiatry, exist to advise on psychotropic prescribing to effectively treat mental health conditions whilst minimising medication adverse effects. Implementation of psychiatric guidelines have, in the past, demonstrated little and transient impact on clinical practice. How effective prescribing guidelines are in aligning practice with evidence currently is unknown and this systematic review aimed to investigate said efficacy. Literature searches were performed on MEDLINE, EMBASE, and CINAHL up to September 2019 and articles were selected by two reviewers independently with discrepancies resolved by a third reviewer. The review identified 18 eligible articles pertaining to the following conditions: depressive disorders, psychotic disorders, post-traumatic stress disorder, anxiety disorders, bipolar affective disorder, attention deficit/hyperactivity disorder, borderline personality disorder, and opiate addiction with depression guidelines being the most frequently evaluated. Seven studies revealed guidelines effected no change in psychotropic prescribing. The remaining studies illustrated that even when practice was changed, the effect was generally small, emphasising the need to change guideline development and implementation, taking into account obstacles or opportunities specific to psychotropic pharmacotherapy.

1. Introduction It is imperative in mental health settings that treatments are aligned with the best available evidence for the specific disorder. As a result, Clinical Practice Guidelines (CPGs) are developed, derived from said evidence with the aim of guiding clinical decision-making to maximise patient outcomes (Institute of Medicine, 2011). A key part of this is to ensure patients receive treatments with favourable risk-benefit profiles while avoiding those that are unnecessary or even deleterious (National Health Medical Research Council, 1999). The quality of these guidelines determines the quality of care provided. Therefore, stringent standards exist by which CPG developers must adhere (Institute of Medicine, 2011; National Health Medical Research Council, 2016; National Institute for Health Care Excellence, 2014; Scottish Intercollegiate Guidelines Network et al., 2008). These standards comment on various aspects including transparency of development, development group composition, and crucially, the systematic review of scientific evidence. CPGs form one of the pillars of evidencebased practice, the others being clinician experience and patient values,

⁎

which altogether aim to maximise patient satisfaction and treatment outcomes (Emparanza et al., 2015; Lugtenberg et al., 2009). CPGs take considerable time, resources, and money to develop, and in other fields of medicine, have proven effective in improving outcomes and the process of care delivery when subjected to rigorous evaluations (Bauer et al., 2009; Grimshaw et al., 1995; Grimshaw and Russell, 1993; Murad, 2017; Ricken et al., 2011). In a systematic review on implementation of psychiatric guidelines however, it was identified that changes to clinical practice were often small and transient (Weinmann et al., 2007). Mental health treatment often involves psychotropics, which can subject patients to a wide array of potential potent side-effects with consequences on treatment adherence and physical health (Leucht et al., 2013; Mago, 2016). It is therefore of substantial importance that clinician practice in this field aligns with the evidence base to ensure better outcomes for individuals affected by mental health disorders. This systematic review aims to examine whether the existence of psychotropic prescribing CPGs can influence a change in mental health prescribing practice.

Corresponding author at: Orygen Youh Health, 35 Poplar Rd, Parkville, VIC 3052, Australia. E-mail address: [email protected] (B. O'Donoghue).

https://doi.org/10.1016/j.psychres.2019.112671 Received 9 July 2019; Received in revised form 29 October 2019; Accepted 31 October 2019 0165-1781/ © 2019 Published by Elsevier B.V.

Please cite this article as: Tony Nguyen, et al., Psychiatry Research, https://doi.org/10.1016/j.psychres.2019.112671

Psychiatry Research xxx (xxxx) xxxx

T. Nguyen, et al.

2. Methods

2.5. Data screening

2.1. Search strategy

Titles and abstracts of papers were screened independently by two reviewers as per selection criteria. Papers that met the criteria then had full articles screened. Discrepancies between reviewers were discussed and resolved by a third reviewer where necessary.

Literature searches were performed on MEDLINE, EMBASE, and CINAHL with the latest search being performed on 16th September 2019. Below is the search performed on MEDLINE. Italicised terms are ‘Subject Headings’, all of which were ‘exploded’ where applicable and were conjoined via the Boolean operator ‘OR’ (in bold below). Searches for EMBASE and CINAHL are detailed in the Appendix. MEDLINE search:

2.6. Data extraction A standardised form was used to extract data from the eligible studies and included: study citation, country of origin, setting, sample size, disorder of interest, the guideline evaluated, primary results, and quality of study.

1 Mental health* OR Mental illness* OR Mental disorder* OR Depression OR Depressive disorder* OR Anxiety OR Anxiety disorder* OR Psychosis OR Psychotic disorder* OR Mental Disorders 2 Clinical practice guideline* OR Clinical guideline* OR Practice guideline* OR Prescribing guideline* OR Prescribing recommendation* OR Treatment guideline* OR Practice guidelines as a topic 3 Clinical practice* OR Practice pattern* OR Guideline adherence* OR Guideline concordance* OR Prescribing pattern* OR Prescribing trend* OR Guideline adherence OR Physicians’ practice patterns 4 Prescri* OR Psychotrop* OR Antidepressant* OR Anti-depressant* OR Antipsychotic* OR Anti-psychotic* OR Anxiolytic* OR Mood stabili?er* OR Psychotropic drugs OR Tranquilizing agents 5 1 AND 2 AND 3 AND 4

2.7. Determination of CPG effect CPGs were determined to have influenced prescribing practice if a change in the direction of guideline recommendations was reported. Presence of an effect was classified as either ‘yes’ or ‘no’, independent of the magnitude of change. 2.8. Quality assessment of studies reviewed All articles reviewed were subject to quality assessment. The quality assessment tool for controlled intervention studies and before-after studies with no control group were used to assess the quality of studies included (National Heart Lung and Blood Institute, 2019). This tool was developed by the National Heart, Lung, and Blood Institute along with other tools to allow for the assessment of multiple quantitative study designs. The tools facilitate the independent evaluation of 14 and 12 components, respectively, which included stated purpose, study population, study design, risks of bias, and limitations. The tools are designed to help reviewers focus on key concepts for evaluating the internal validity of a study. They are not intended to create a list that is tallied up to arrive at a summary judgement of quality, rather it encourages critical appraisal of the study before concluding whether the quality of the study is ‘good’, ‘fair’, or ‘poor’. Quality assessments were performed independently by two reviewers and a consensus was reached without requirement of a third reviewer. In this review, quality assessments were used to consider the quality of the review broadly and inform discussion of the current body of evidence surrounding CPG efficacy.

2.2. Inclusion and exclusion criteria Articles were included for review if they satisfied the following criteria: i Evaluated a clinical practice guideline in relation to psychotropic prescribing (e.g. pre- and post- study, or where data allowed for evaluation even if it was not the primary objective). ii Were related to a mental health disorder. iii Had an outcome related to prescribing in clinical practice. iv Were published in English. Articles were excluded for review if they: i Evaluated the following conditions: chronic pain disorders, dementia, Alzheimer's, or ii Used subjective data (e.g. surveys of clinician opinion).

3. Results 3.1. Search results

2.3. Definition

After duplicate removal of final search results, a total of 1847 articles were identified. Title and abstract screening reduced the number of articles to 44. Following full article review, 18 were determined to fulfil the inclusion and exclusion criteria. This process is presented in Fig. 1. The 18 articles covered the evaluation of guidelines relating to various mental health conditions (Table 1). Seven investigated the effects of guidelines for depression, three for psychosis, two for bipolar affective disorder, and two for post-traumatic stress disorder. Only one study was identified for each of the following: attention deficit/hyperactivity disorder, borderline personality disorder, and opiate addiction. One study evaluated both generalised anxiety disorder and social phobia guidelines. Details are summarised in detail in Table 1.

The definition of a ‘clinical practice guideline’ for the purposes of article identification in this review was the one used by Australian Clinical Practice Guidelines (Australian Clinical Practice Guidelines, 2017) and the US National Guideline Clearinghouse (National Guideline Clearinghouse, 2018): “Clinical Practice Guidelines are evidence-based statements that include recommendations intended to optimise patient care and assist health care practitioners to make decisions about appropriate health care for specific clinical circumstances. Clinical Practice Guidelines should assist clinicians and patients in shared decision making.” 2.4. Data retrieval

3.2. CPGs in the treatment of depression

The data retrieved by the database searcher was uploaded to the referencing manager EndNote (https://endnote.com/). EndNote was then used to remove duplicates from the review's sample.

Seven studies examined the impact of CPGs for the treatment of depression. The 2004 NICE guideline discouraged antidepressant use for incident depression (National Institute for Clinical 2

Psychiatry Research xxx (xxxx) xxxx

T. Nguyen, et al.

This period saw an increasing trend in fluoxetine prescription, albeit, not statistically significant, in the context of an overall decrease in SSRI use in young people (2002: 4.74/1000 population, 2008: 2.61/1000 population) as per Irish Medical Board recommendations. As fluoxetine possesses the largest evidence base for pharmacotherapy of youth depression, NICE guidelines recommend it be the first-line antidepressant medication for young people (National Institute for Health and Care Excellence, 2005). In South London, a case note review of 93 patients on antidepressants in a threeyear period was conducted within a child and adolescent mental health service (Perera et al., 2007). While limited by sample size, over the study period, an increase in the proportion of fluoxetine use as an antidepressant was observed (9/13 in 2003, 24/25 in 2006), in accordance with guideline recommendations. Another study evaluated guidelines for youth depression in the Netherlands, where low-dose fluoxetine is the advised first-line pharmacotherapy followed by citalopram or sertraline in poor responders (Landelijke Stuurgroep Multidisciplinaire Richtlijnontwikkeling in de GGZ, 2009; Vries et al., 2016). Data from a Dutch pharmacy prescription database totalling 2942 outpatients over a 10-year period was analysed to assess the impact of the CPG (Vries et al., 2016). Five years post-guideline, fluoxetine use increased (10.1% pre, 19.7% post) but the most commonly prescribed antidepressant was citalopram. A difference was observed in drug choice between specialties, with specialists prescribing fluoxetine more often (21.5%) than GPs (15.8%). The study also found starting doses to be divergent from recommendations with a large proportion of patients, especially older children, being initiated on adult doses rather than the advised quarter dose. The starting doses were stable throughout the study period except for citalopram which saw a decrease (1 adult dose pre, 0.4 adult dose post).

Fig. 1. Article screening process.

Excellence, 2004). This guideline was evaluated via time trend analysis in a general practice (GP) setting using data for 237,178 depression episodes over a 10-year period from the Clinical Practice Research datalink in England (Kendrick et al., 2015). Prescribing changed over the study period as per recommendations, decreasing from 72.5% to 61% following the introduction of the CPGs. The authors comment that it was possible that the reduction may have been contributed to by the GP performance management system, the Quality Outcomes Framework (QOF), introduced in 2006, although they found that there was still a reduction in the prescribing for incident depression in the interval between introduction of the CPG and QOF. In Taiwan in 2004, guidelines were produced to reduce benzodiazepine use in the treatment of depression given the lack of evidence supporting this practice (Department of Health, 2004; National Institute for Health and Care Excellence, 2009). To determine the impact of recommendations, retrospective longitudinal trend analysis was performed with inpatient and outpatient treatment data from 1,000,000 insurance beneficiaries obtained from the Taiwan Longitudinal Health Insurance Database (Lai et al., 2011). Over a three-year period covering both pre and post-guideline introduction, no significant decrease was observed in inpatient (7–11.8% pre, 7.8–12.6% post) or outpatient settings (6.7–9.4% pre, 8.0–9.4% post). However, inter-disciplinary differences were noted with psychiatry having the lowest non-compliance rate while internal medicine possessed the highest. Due to concerns regarding inadequate dose prescribing of antidepressants, a randomised control trial assessed the efficacy of guidelines in increasing doxepin doses prescribed by GPs and private psychiatrists in Germany (Linden and Schotte, 2007). The guideline, recommending doses of 150 mg/d, was distributed to the experimental group in the form of detailed initiation and up-titration instructions. Data from 1319 patients receiving doxepin revealed a higher average dose in the intervention group (95 mg/d) than the control group (83 mg/d) but was still short of the recommended 150 mg/d. The 1998 American Academy of Child and Adolescent Psychiatry CPG recommended selective serotonin reuptake inhibitors (SSRIs) as first-line pharmacotherapy while discouraging tricyclic antidepressants (TCAs) (Birmaher et al., 1998). Data on office-based visits of children and adolescents with a depression diagnosis were derived from the US National Ambulatory Medicare Care Survey for retrospective crosssectional analysis (Skaer et al., 2009). A change in prescribing patterns in accordance with guidelines was seen with TCAs decreasing from 21% to 2.7% of total antidepressant prescriptions and SSRIs increasing from 20.7% to 39.7% following introduction. In 2003, the Committee for Safety of Medicines issued advice against treatment of depression in young people with SSRIs other than fluoxetine due to potential increased suicidality risk (Wijlaars et al., 2012). This advice was adopted by the Irish Medical Board and a study to evaluate its effect on prescribing practice was conducted, utilising Irish pharmacy claims data for 2002 to 2011 (O'Sullivan et al., 2015).

3.3. CPGs in the treatment of psychosis Three studies evaluated guidelines relating to antipsychotics and psychotic disorders. Following evidence of cardiac risks from thioridazine, an antipsychotic, the Committee for Safety of Medicines updated their recommendations, restricting the drug to second-line schizophrenia treatment and communicated this via fax in December 2000 (Wright et al., 2004). Time series analysis was performed on prescribing data from 444 GPs in Leeds obtained via the electronic Prescribing Analysis and Cost system (Wright et al., 2004). The 16 months following this advice saw a significant drop in thioridazine prescription (810 prescriptions per month) and a counter increase in haloperidol prescription (120 prescriptions per month). Another study evaluated a 2011 hospital-based practice policy advising against antipsychotic polypharmacy and high-dose therapy was performed using inpatient records at an Irish general psychiatric hospital (281 patients pre, 239 patients post-guideline) (Kelly et al., 2014; St Patrick's University Hospital, 2011). This identified that despite an increase in multiple concurrent second-generation antipsychotic (SGA) use, overall, there was a significant decrease in polypharmacy (27% pre, 16% post). Furthermore, a decrease in high dose therapy in patients with psychotic disorders was identified (5/13 patients pre, 0/10 patients post). The Choosing Wisely campaign is an international program aimed at eliminating low-value treatments via national lists of succinct evidencebased recommendations (Brett et al., 2017). These vary between countries but a common one is the avoidance of concurrent use of multiple antipsychotics (Brett et al., 2017; Choosing Wisely, 2013). In April 2015, the campaign was launched in Australia and data from the Australia Pharmaceutical Benefits Scheme was used to quantify impacts on prescribing practice (Brett et al., 2018). The rates of antipsychotic polypharmacy throughout the study period from 2013 to 2016 remained unchanged at 0.2%. 3

4

Taiwan

UK

USA

USA

Ireland

(Lai et al., 2011)

(Vasudev and Mead, 2010)

(Bernardy et al., 2012)

(Hawkins et al., 2012)

(Kelly et al., 2014)

Germany

(Linden and Schotte, 2007)

USA

UK

(Strang et al., 2007)

(Skaer et al., 2009)

USA

(Vasile et al., 2005)

UK

UK

(Wright et al., 2004)

(Perera et al., 2007)

Location

Study

Adult general psychiatric hospital

VISN20

Inpatients and outpatients

Female psychiatric inpatients

US National Ambulatory Medical Care Survey Inpatients and outpatients

Child and adolescent mental health service

GP and private psychiatric practices

Community pharmacies

Harvard/Brown Anxiety Disorders Research Project

GP practices

Setting

281 patients pre, 239 patients post-CPG

64,872 patients

498,081 patients by 2009

48 patients

1000,000 insurance beneficiaries

Millions of ‘office-based’ visits

93 patients

1319 patients

3732 prescriptions pre, 9620 prescriptions postCPG

305 Generalised anxiety disorder (GAD), 232 Social phobia (SP) patients at end of study

444 GPs

Sample size (N)

No specific disorder

Post-traumatic stress disorder

Post-traumatic stress disorder ICD-9 309.81

Bipolar affective disorder

Depression ICD-9-CM 296.2x, 296.3x

Depression ICD-9-CM 296.2–296.36, 300.4, 311

Depression

International Classification of Diseases (ICD)−10 depressive symptoms

Opiate addiction

Generalised anxiety disorder, Social phobia

Schizophrenia

Disorder

Table 1 Articles reviewed, detailing location, setting, disorder, guideline evaluated, main findings, and study quality.

Prescribing and monitoring of antipsychotic medication, including high dose antipsychotic

Bipolar disorder: the management of bipolar disorder in adults, children and adolescents, in primary and secondary care (National Institute for Health and Clinical Excellence, 2006) Clinical practice guideline for the management of post-traumatic stress (The Management of Posttraumatic Stress Disorder Working Group, 2004) Clinical practice guideline for the management of post-traumatic stress (The Management of Posttraumatic Stress Disorder Working Group, 2004)

Summary of the practice parameters for the assessment and treatment of children and adolescents with depressive disorders (Birmaher et al., 1998) Guidelines for benzodiazepine using in sedation and hypnosis (Department of Health, 2004)

Depression in children and young people (National Institute for Health and Care Excellence, 2005)

Guideline on doxepin prescribing in daily practice (Linden and Schotte, 2007)

Consensus statement on social anxiety disorder from the International Consensus Group on depression and anxiety (Ballenger et al., 1998) Consensus statement on GAD from the international consensus group on depression and anxiety (Ballenger et al., 2001) Department of Health Taskforce report (Her Majesty's Stationary Office (HMSO), 1996) Reducing Drug-Related Deaths (Advisory Council on the Misuse of Drugs, 2000) Department of Health Orange Guidelines (Gabbay and Carnwath, 2000; Her Majesty's Stationary Office (HMSO), 1999; Keen, 1999; Robertson, 2000; Strang, 1999)

CSM advice on thioridazine (Breckenridge, 2000)

Guideline evaluated

Yes

No

Yes

No

No

Yes

Yes

Yes

Yes

Yes

Yes

Change

Fair

Good

Fair

Fair

Good

Good

Fair

Fair

Good

Fair

Fair

Quality

(continued on next page)

Increased 'all benzodiazepine use' (Females: 31.2% pre, 38.8% post. Male: 25% pre, 26% post). Increased chronic use, defined as > 90 days’ supply (Females: 18% pre, 22.7% post. Males: 15.4% pre, 16.4% post). Decreased antipsychotic polypharmacy (2008: 45/161, 2012: 21/131, p: 0.02).

Decreased benzodiazepine use (6.1%).

Unchanged benzodiazepine monotherapy rate (Outpatient: 6.7 to 9.4% pre, 8.0 to 9.4% post, p: 0.083; Inpatient: 7.0 to 11.8% pre, 7.8 to 12.6% post, p: 0.925). Unchanged valproate prescription rate (15/32 patients pre, 7/16 patients post).

Decreased thioridazine prescription (810 items per month, 95%CI: −1200 to −420, p: <0.001). Increased haloperidol prescription (120 items per month, 95%CI: 60 to 180, p: <0.001). Increased SSRI/SNRI monotherapy (GAD: 15%, SP: 14%). Decreased benzodiazepine monotherapy (GAD: 17%, SP: 25%). Increased polypharmacy with concurrent SSRI/SNRI and benzodiazepine (GAD: 12%, SP: 16%). Increased use of relevantly licenced drugs (increase from 97% to >99%), higher doses (mean daily dose increased from 47.3 mg to 56.3 mg), increased daily dispensing (22% increase), increased supervised consumption (36% increase), and reduced methadone tablet and ampoule prescription (9.15% decrease in tablets, 7.45% decrease in ampoules). Decreased GP provision of treatment (11% decrease). Increased doxepin doses prescribed in intervention group (12 mg/day higher average max daily dose in the intervention group). Increased fluoxetine prescription as a proportion of total antidepressants (2003: 9/18, 2004: 19/21, 2005: 22/29, 2006: 24/25 cases). Decreased TCA prescriptions (from 21% to 2.7% of total antidepressants prescribed). Increased SSRI use (from 20.7% to 39.7%).

Results

T. Nguyen, et al.

Psychiatry Research xxx (xxxx) xxxx

5

USA

Spain

(Fiks et al., 2016)

(Martin-Blanco et al., 2017)

Scotland

Netherlands

(Vries et al., 2016)

(Lyall et al., 2019)

Ireland

(O'Sullivan et al., 2015)

Australia

UK

(Kendrick et al., 2015)

(Brett et al., 2018)

Location

Study

Table 1 (continued)

Inpatients and outpatients

Outpatients

Outpatients

GP practices

Outpatients

Irish General Medical Services scheme

GP practices

Setting

10% of all people ≥ 18 years within the PBS 23,135 patients

457 patients

211,558 visits

2942 patients

Ranging between 188,833 to 311,579 children over the study period

237,178 episodes of depression

Sample size (N)

Bipolar affective disorder ICD-10 codes: F30, F31, F38.9 ICD-9 codes: 296.0–296.1, 296.4–296.89 Excluding ICD-10 F31.8; ICD-9 296.8

Psychosis

Borderline personality disorder meeting DSM-IV criteria

Attention deficit / hyperactivity disorder ICD-9 314.0–314.9

Depression

Depression

Depression

Disorder

APA (American Psychiatric Association (APA), 2001) Dutch (Landelijke Stuurgroep Multidisciplinaire Richtlijnontwikkeling in de GGZ, 2008), German (DGPPN, 2009), NICE (National Collaborating Centre for Mental Health, 2009), Spanish (GPC, 2011), Danish (Danish Health Authority, 2017), and Australian (National Health Medical Research Council, 2012) borderline personality disorder guidelines Choosing Wisely prescribing practices lists. (Brett et al., 2017; Choosing Wisely, 2013) Assessment and management of bipolar disorder: summary of updated NICE guidance. (Kendall et al., 2014)

Unchanged antipsychotic polypharmacy rate (0.2% throughout) Valproate use in women declined (OR: 0.93, 95%CI: 0.90 to 0.97), but increased in men (OR: 1.11, 95%CI: 1.04 to 1.18), leading to an overall increase (OR: 1.34, 95%CI: 1.32 to 1.36).

Increased fluoxetine prescription (9.6%). Unchanged rate of high-dose antidepressant initiation except for citalopram (Citalopram: 1 adult dose pre, 0.4 adult dose post). Unchanged stimulant prescription rate overall (0.4% of practice visits). Interpractice variation in changes (increased at 22% of practices, decreased at 41%, and stable at 21%). Unchanged polypharmacy rate (53.8% on ≥ 3 psychotropics, p: 0.187).

Decreased SSRI prescription (2002: 4.74/ 1000 population, 95%CI: 4.47 to 5.01; 2008: 2.61/1000 population, 95%CI: 2.43 to 2.80).

Decreased high-dose therapy in psychotic disorders (2008: 5/13, 2012: 0/10, p: 0.05). Decreased pharmacotherapy for incident depression (11.5%).

medication (St Patrick's University Hospital, 2011) Depression: Management of depression in primary and secondary care (National Institute for Clinical Excellence, 2004) Selective serotonin reuptake inhibitors (SSRIs): overview of regulatory status and CSM advice relating to major depressive disorder (MDD) in children and adolescents including a summary of available safety and efficacy data (Committee on Safety of Medicines, 2003) Multidisciplinaire richtlijn Addendum Depressie bij Jeugd [Dutch multidisciplinary guideline addendum for depression in youth] (Landelijke Stuurgroep Multidisciplinaire Richtlijnontwikkeling in de GGZ, 2009) ADHD: clinical practice guideline for the diagnosis, evaluation and treatment of AD/HD in children and adolescents (Wolraich et al., 2011)

Results

Guideline evaluated

No

No

No

No

Yes

Yes

Yes

Change

Good

Good

Good

Good

Fair

Good

Good

Quality

T. Nguyen, et al.

Psychiatry Research xxx (xxxx) xxxx

Psychiatry Research xxx (xxxx) xxxx

T. Nguyen, et al.

3.4. CPGs in the treatment of bipolar affective disorder

change in psychotropic profile in accordance with CPGs (Vasile et al., 2005). SSRI/SNRI monotherapy increased (GAD: 6% pre, 21% post; SP: 8% pre, 22% post) while benzodiazepine monotherapy decreased (GAD: 49% pre, 32% post; SP: 47% pre, 22% post). There was however an increasing proportion of patients on concurrent antidepressant and benzodiazepine treatment, contrary to guidelines (GAD: 12% pre, 24% post. SP: 9% pre, 25% post). The proportion of unmedicated patients remained stable throughout the study.

Two studies evaluated guidelines for bipolar affective disorder prescribing. A case note review of 48 female psychiatric wards patients was conducted to investigate prescribing changes recommended by NICE guidelines discouraging use of teratogenic valproate in females of child-bearing age (National Institute for Health and Clinical Excellence, 2006; Vasudev and Mead, 2010). In the 15 months following guideline publication, there was no significant change to the proportion of patients receiving valproate (15/32 pre, 7/16 post). In this context and subject to the limitations of a very small sample size, a guideline-initiated change in prescribing practice was not identified. A larger study of prescribing in bipolar affective disorder was conducted in Scotland (Lyall et al., 2019), evaluating the 2014 updated NICE guideline which changed recommendations, advising first-line treatment only be with lithium monotherapy (Kendall et al., 2014). Linkage of prescribing data and electronic Scottish Morbidity Records of patients prescribed psychotropics between 2009 and 2016 identified prescribing practices and trends largely in opposition to guidelines. During the study period, lithium monotherapy was the fifth most common treatment (5.90%), behind antidepressant monotherapy, antipsychotic monotherapy, hypnotic/anxiolytic monotherapy, and antidepressant/antipsychotic combined therapy respectively. The proportion of patients treated with lithium also declined each year (OR: 0.83, 95%CI: 0.82 to 0.85). Contrasting the trend observed by Vasudev and Mead (2010), was a declining use of valproate in women (OR: 0.93, 95%CI: 0.90 to 0.97), but this was countered by an increased use in men (OR: 1.11, 95%CI: 1.04 to 1.18) leading to an overall increase, going against guideline recommendations.

3.7. CPGs in the treatment of other mental health conditions One study was identified for each of the following mental health conditions: attention deficit/hyperactivity disorder, borderline personality disorder, and opiate addiction. Guidelines for preschool-aged children with attention deficit/hyperactivity disorder introduced by the American Academy of Pediatrics recommended consideration of stimulants, such as methylphenidate, should response to behavioural therapy be inadequate (Wolraich et al., 2011). Evaluation of the CPG in the GP setting used retrospective data from 211,558 practice visits obtained from a network of electronic health records (Fiks et al., 2016). The study identified that in the three years following introduction, rates of stimulant prescription were overall, unchanged (0.4% of all practice visits). However, significant inter-practice variation was noted with prescription having increased at 22% of practices, decreased at 41%, and remained stable at 21%. These differences did not correlate with urbanicity, regionality, or network affiliation. The various guidelines for borderline personality disorder globally, released between 2008 and 2012, disagree regarding pharmacotherapy for symptomatic control but are in consensus that polypharmacy should be avoided (American Psychiatric Association (APA), 2001; Danish Health Authority, 2017; DGPPN, 2009; GPC, 2011; Landelijke Stuurgroep Multidisciplinaire Richtlijnontwikkeling in de GGZ, 2008; Lieb et al., 2010; National Collaborating Centre for Mental Health, 2009; National Health Medical Research Council, 2012). A retrospective, cross-sectional observational study with 457 patients with borderline personality disorder from Spanish outpatient services identified no change in polypharmacy post-guidelines (MartinBlanco et al., 2017). While the prescribing patterns changed (decreased TCA and benzodiazepine use, increased SGA use), polypharmacy remained prevalent and stable (53.8% on ≥ 3 psychotropics, p: 0.187) over the 15-year study period. The proportion of polypharmacy was 42% in patients with no other psychiatric comorbidities. In England, many CPGs surrounding substitute opiates for addiction were released from 1996 to 2000 (Advisory Council on the Misuse of Drugs, 2000; Gabbay and Carnwath, 2000; Her Majesty's Stationary Office (HMSO), 1996, 1999; Keen, 1999; Robertson, 2000; Strang, 1999; Strang et al., 2007). Community pharmacy data collected from a national survey at two time points (3732 prescriptions in 1995, 9620 prescriptions in 2005) were analysed to determine the impact on prescribing practice (Strang et al., 2007). Changes in line with advice were seen for six of seven recommendations: increased use of relevantly licenced agents (97% pre, 99.1% post), increased methadone dose (Pre: 47.3 mg mean daily dose, 27.5% of doses in recommended range. Post: 56.3 mg mean daily dose, 40.1% of doses in recommended range.), increased daily dispensing (41.2% pre, 58.5% post), increased supervised consumption (0% pre, 35.7% post), decreased prescription of methadone in tablet form (10.9% pre, 1.75% post), and decreased prescription of injectable methadone ampoules (9.3% pre, 1.85% post). Contrary to CPGs, however, was the decrease in the proportion of patients receiving treatment from a GP (41% pre, 30% post).

3.5. CPGs in the treatment of post-traumatic stress disorder Two studies evaluated the 2004 US Veteran Affairs (VA) and Department of Defense post-traumatic stress disorder guideline which recommended SSRIs and serotonin-noradrenaline reuptake inhibitors (SNRIs) and discouraged benzodiazepines (The Management of Posttraumatic Stress Disorder Work Group, 2017; The Management of Posttraumatic Stress Disorder Working Group, 2004). The number of patients being treated for post-traumatic stress disorder through the VA healthcare system was 170,685 in 1999 and increased to 498,081 in 2009 (Bernardy et al., 2012). Analysis of all outpatient contacts, inpatient discharges, and pharmaceutical utilisation data from 1999 to 2009 showed an increase in SSRI/SNRI use (49.7% pre, 58.9% post), a decrease in antipsychotic use (20% pre, 13.95% post), and a decrease in benzodiazepine use (36.7% pre, 30.6% post), all in accordance with guidelines (Bernardy et al., 2012). A guideline evaluation was also performed by Hawkins et al. (2012) with administrative data from the VISN20 network, a subset of the Veterans Health Administration covering four states in the northwest US. Retrospective analysis of data from 64,872 patients revealed a small but statistically significant increase in all benzodiazepine use (Females: 31.2% pre, 38.8% post. Male: 25% pre, 26% post) as well as chronic use (Females: 18% pre, 22.7% post. Males: 15.4% pre, 16.4% post), here defined as greater than 90 days’ supply. 3.6. CPGs in the treatment of anxiety disorders One study evaluated guidelines for both generalised anxiety disorder (GAD) and social phobia (SP). Guidelines from the International Consensus Group on Depression and Anxiety for generalised anxiety disorder and social phobia advise restriction of benzodiazepines to acute anxiety or adjunctive use in exacerbations while primary pharmacotherapy should be with SSRIs or SNRIs (Ballenger et al., 1998, 2001). Prospective longitudinal analysis of 305 patients with generalised anxiety disorder and 232 patients with social phobia from the Harvard/Brown Anxiety Disorders Research Project in the US showed a

3.8. Quality of studies Our review of the quality of studies found that studies were generally of a high standard with ten identified as ‘good’ and eight as ‘fair’. 6

Psychiatry Research xxx (xxxx) xxxx

T. Nguyen, et al.

The quality of many studies could be attributed to the use of large datasets of patient records, however several limitations of using these data exist. First, there is often missing information and patient records may not include details regarding care received from other health providers. Second, prescribing information often did not include information on the indication so whether a patient was receiving a medication for the focus diagnosis or a comorbid condition could not be known. Additionally, whether the prescribing of a medication was appropriate for the patient's condition and severity could not be adequately concluded from the data available to the researchers. Thirdly, there was often no information regarding actual medication use outside of what a patient was prescribed so actual doses used or compliance was not known. Last, many of the studies were naturalistic, observational in design. Therefore, causality is hard to establish due to various potential confounders both unknown and known that may have affected results, one such being the concurrent change in the benzodiazepine prescribing policy in the study by Kelly and colleagues (2014). Although, the studies included in this review tended to have clearly defined objectives, eligibility criteria, pre-specified outcomes and, as stated, used large datasets.

around $50,000 USD per guideline (Okechukwu, 2019) while the NICE allocates around $12,000,000 USD to the directorate under which guidelines are produced (National Institute for Health and Care Excellence, 2019). The results from this review indicate that the existence of guidelines themselves, in a naturalistic setting, are often insufficient for translating evidence to clinical practice. Clearly, considerable efforts need to be allocated to strategies to increase guideline compliance in prescribing practices across mental health disorders. The barriers to successful CPG uptake are diverse, including factors inherent in the guidelines themselves, the attitudes of individual clinicians, and organisations’ ability to integrate guidelines into local policies (Fischer et al., 2016). Implementation strategies are required to address and overcome these barriers. The utility of implementation strategies in the sphere of psychiatric guidelines was investigated by Weinmann et al. (2007). It was identified that a scarcity of implementation studies for psychiatric guidelines existed and, in those few studies, a change in practice was often minimal or transient. This leaves room for further research into effective implementation of guidelines. From this study, we see that the translation of research into clinical psychotropic prescribing practice is far from ideal. Given the focus on just one aspect of mental health treatment, it is possible to address barriers specific to this context. Mental health treatment, unlike with physical health conditions, lacks the availability of blood markers and pathology results upon which to base primary treatment decisions. Having guidelines require screens or tests of symptomatology and severity may possibly serve an analogous purpose in guiding appropriate treatment choices as seen with the validated severity screen required by the UK QOF in GP treatment of depression (Kendrick et al., 2015). Furthermore, with medication approvals and availabilities varying between countries and treatment settings, CPGs need to consider their intended target and the feasibility by which clinicians can adhere to their recommendations. The lesser magnitude of practice change from Dutch youth depression guidelines compared to NICE guidelines were possibly, as noted by Vries et al. (2016), contributed to by medication availability not allowing for easy guideline-concordant prescribing (Vries et al., 2016). The environment in which a guideline is released and the logistics for adherence should therefore be considered in development and evaluation. Lastly, with electronic health records and the accessibility and objectivity of prescribing information relative to other clinical data, the evaluation of CPGs pertaining to psychotropic prescribing is easier to do than those for other aspects of mental health treatment. In other areas of medicine, such auditing and feedback have demonstrated utility to bringing clinical practice in line with the evidence base (Fischer et al., 2016). Therefore, the benefit of necessitating routine evaluations of prescribing practice as part of a psychotropic prescribing guideline should be considered in its development. With the move to evidence-based medicine, CPGs stand as a precious tool that synthesises the vast body of scientific literature into succinct recommendations for clinicians. As with any tool however, it must be employed correctly. While mental health treatment is multimodal and interdisciplinary, the specific aspect of pharmacotherapy presents some unique challenges and opportunities which may be addressed to increase clinician compliance to practice guidelines. Identifying ways to take advantage of those opportunities and overcome those barriers would prove invaluable for guideline developers, clinicians, and ultimately, patients.

4. Discussion 4.1. Main findings The main findings of this review were that there were few attempts to evaluate the impact of guidelines on clinical practice in psychiatry and that guidelines themselves can differ in their effect on prescribing practice. Seven of 18 CPG evaluations identified no impact while the others were successful in instrumenting change, albeit, often to a minimal extent. This contrasts with systematic reviews of general medical CPGs where the vast majority of guidelines had a significant impact on clinical practice (Grimshaw et al., 1995; Grimshaw and Russell, 1993). This indicates that within psychiatry, further work is needed to translate research to the patient care level and as per the findings of Weinmann and colleagues (2007), make it sustainable. Guidelines developed for the treatment of depression were the most frequently evaluated. In the studies evaluating adult depression treatment, two of three studies saw practice changes following guidelines. In the treatment of youth depression however, all four studies saw favourable responses. A hospital antipsychotic prescribing policy led to a decrease in polypharmacy and high dose therapy and the Committee for Safety of Medicines recommendations in Leeds saw decreased prescription of thioridazine by GPs. Conversely, the Choosing Wisely campaign did not reduce antipsychotic polypharmacy rates in Australia. Post-traumatic stress disorder and bipolar affective disorder were the next most common disorders in which guidelines were evaluated. In post-traumatic stress disorder the prescribing pattern changed with increased SSRI/SNRI use but conflicting results surround benzodiazepine use. A study focusing on a regional subset of veterans identified an increase in benzodiazepine use while another study using national US data saw a decrease. In bipolar affective disorder, one study suggested guidelines were ineffective at reducing valproate use in child-bearing aged females. In another study, the trend was the opposite, but this was countered by an overall increase in valproate use contrary to first-line lithium recommended by guidelines. In anxiety disorders, benzodiazepine use has declined in accordance with guidelines with increased utilisation of SSRIs/SNRIs. In the treatment of attention deficit/hyperactivity disorder in children, stimulant prescription rates overall, remained unchanged by guidelines. The use of opiate substitutes in addiction treatment largely responded well to English recommendations.

4.3. Limitations

4.2. Clinical implications

The results of this systematic review must be viewed in light of limitations of the search process. Only three major databases were searched. Perhaps extending the search beyond major databases and into grey literature, other studies may have been identified. A further

CPGs are a resource intensive endeavour to develop, with financial cost estimates from the American Academy of Pediatrics suggested to be 7

Psychiatry Research xxx (xxxx) xxxx

T. Nguyen, et al.

limitation of this review was that it was not registered online on a database such as PROSPERO prior to its undertaking.

American Psychiatric Association (APA), 2001. Practice guideline for the treatment of patients with borderline personality disorder. Am. J. Psychiatry 158 (Suppl10), 1–52. Australian Clinical Practice Guidelines, 2017. Clinical Practice Guidelines Portal. National Health and Medical Research Council. Ballenger, J.C., Davidson, J.R., Lecrubier, Y., Nutt, D.J., Bobes, J., Beidel, D.C., Ono, Y., Westenberg, H.G., 1998. Consensus statement on social anxiety disorder from the international consensus group on depression and anxiety. J. Clin. Psychiatry 17 (59 Suppl), 54–60. Ballenger, J.C., Davidson, J.R., Lecrubier, Y., Nutt, D.J., Borkovec, T.D., Rickels, K., Stein, D.J., Wittchen, H.U., 2001. Consensus statement on generalized anxiety disorder from the international consensus group on depression and anxiety. J. Clin. Psychiatry 11 (62 Suppl), 53–58. Bauer, M., Pfennig, A., Linden, M., Smolka, M.N., Neu, P., Adli, M., 2009. Efficacy of an algorithm-guided treatment compared with treatment as usual: a randomized, controlled study of inpatients with depression. J. Clin. Psychopharmacol. 29 (4), 327–333. Bernardy, N.C., Lund, B.C., Alexander, B., Friedman, M.J., 2012. Prescribing trends in veterans with posttraumatic stress disorder. J. Clin. Psychiatry 73 (3), 297–303. Birmaher, B., Brent, D.A., Benson, R.S., 1998. Summary of the practice parameters for the assessment and treatment of children and adolescents with depressive disorders. American Academy Of Child And Adolescent Psychiatry. J. Am. Acad. Child Adolesc. Psychiatry 37 (11), 1234–1238. Breckenridge, A., 2000. Thioridazine: Restricted Indications and New Warnings On Cardiotoxicity. London. Committee on Safety of Medicines. Brett, J., Elshaug, A.G., Bhatia, R.S., Chalmers, K., Badgery-Parker, T., Pearson, S.-A., 2017. A methodological protocol for selecting and quantifying low-value prescribing practices in routinely collected data: an Australian case study. Implement. Sci. 12 (1), 58. Brett, J., Zoega, H., Buckley, N.A., Daniels, B.J., Elshaug, A.G., Pearson, S.-A., 2018. Choosing wisely? Quantifying the extent of three low value psychotropic prescribing practices in Australia. BMC Health Serv. Res. 18 (1), 1009 -1009. Choosing Wisely, 2013. Don't routinely prescribe two or more antipsychotic medications concurrently. Available from: http://www.choosingwisely.org/clinician-lists/ american-psychiatric-association-routine-prescription-of-two-or-more-concurrentantipsychotics/. Accessed September 2019. Committee on Safety of Medicines, 2003. Selective serotonin reuptake inhibitors (SSRIs): overview of regulatory status and CSM advice relating to major depressive disorder (MDD) in children and adolescents including a summary of available safety and efficacy data. Danish Health Authority, Borderline personality disorder guideline. Formerly accessible throughhttps://www.sst.dk/en/publications/2015/~/media/ D39B3600DE4A49DC8D3FF0FC2B8C4B9E.ashxwhen referenced by Martin-Blanco et al.2017, Denmark. Department of Health, Taiwan, 2004. Guidelines for benzodiazepine using in sedation and hypnosis, Taiwan. DGPPN, 2009. Deutsche Gesellschaft für Psychiatry. Psychotherapie und Nervenheilkunde [German guideline for personality disorders]. Emparanza, J.I., Cabello, J.B., Burls, A.J.E., 2015. Does evidence-based practice improve patient outcomes? An analysis of a natural experiment in a Spanish hospital. J. Eval. Clin. Pract. 21 (6), 1059–1065. Fiks, A.G., Ross, M.E., Mayne, S.L., Lihai, S., Weiwei, L., Steffes, J., McCarn, B., Grundmeier, R.W., Localio, R., Wasserman, R., 2016. Preschool ADHD diagnosis and stimulant use before and after the 2011 AAP practice guideline. Pediatrics 138 (6), 23 -23. Fischer, F., Lange, K., Klose, K., Greiner, W., Kraemer, A., 2016. Barriers and strategies in guideline implementation—a scoping review. Healthcare 4 (3), 36. Gabbay, M.B., Carnwath, T., 2000. A cautious welcome for the new guidelines on management of drug dependence. Br. J. General Pract. 50 (451), 92. GPC, 2011. Guía De Práctica Clínica Sobre Trastorno Límite De La Personalidad [Spanish Clinical Practice Guideline On Borderline Personality Disorder]. Barcelona, Spain. Grimshaw, J., Freemantle, N., Wallace, S., Russell, I., Hurwitz, B., Watt, I., Long, A., Sheldon, T., 1995. Developing and implementing clinical practice guidelines. Qual. Health Care 4 (1), 55–64. Grimshaw, J.M., Russell, I.T., 1993. Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations. The Lancet 342 (8883), 1317–1322. Hawkins, E.J., Malte, C.A., Imel, Z.E., Saxon, A.J., Kivlahan, D.R., 2012. Prevalence and trends of benzodiazepine use among veterans affairs patients with posttraumatic stress disorder, 2003-2010. Drug Alcohol Dependence 124 (1/2), 154–161. Her Majesty's Stationary Office (HMSO), 1996. Report of an Independent Review of Drug Treatment Services in England. In: Health, D.o. (Ed.), Report of an Independent Review of Drug Treatment Services in England. London. Her Majesty's Stationary Office (HMSO), 1999. Drug misuse and dependence guidelines on clinical management. Institute of Medicine, 2011. Clinical Practice Guidelines We Can Trust. The National Academies Press, Washington, DC. Keen, J., 1999. Managing Drug Misuse in General Practice: New Department of Health Guidelines Provide a Benchmark for Good Practice. British Medical Journal Publishing Group. Kelly, J., Kelly, F., Santlal, K., O’Ceallaigh, S., 2014. The impact of a change in prescribing policy on antipsychotic prescribing in a general adult psychiatric hospital. Ir. J. Psychol. Med. 31 (3), 167–173. Kendall, T., Morriss, R., Mayo-Wilson, E., Marcus, E., 2014. Assessment and management of bipolar disorder: summary of updated NICE guidance. BMJ 349, g5673. Kendrick, T., Stuart, B., Newell, C., Geraghty, A.W., Moore, M., 2015. Did NICE guidelines and the quality outcomes framework change GP antidepressant prescribing in England? Observational study with time trend analyses 2003-2013. J. Affect. Disord.

5. Conclusion Clinical Practice Guidelines arise from rigorous analysis of evidence to advise clinicians on the best treatment course for patients. Despite the considerable efforts involved in their development, the change they effect in clinical practice in the context of mental health pharmacotherapy is often minimal or insubstantial. In addition to the wellknown barriers to practice guideline adoption in general, trying to change psychotropic prescribing practice comes with its own unique challenges and opportunities. Further work into overcoming the barriers and exploiting advantages by guideline developers is imperative in making clinical practice align with guidelines to ensure patients are provided with the best possible treatment. Declaration of Competing Interest The authors declare that there are no conflicts of interest. Appendix Search strategy Below are searches performed on EMBASE and CINAHL. Italicised terms are ‘Subject Headings’, all of which were ‘exploded’ where applicable. EMBASE search: 1 Mental health* OR Mental illness* OR Mental disorder* OR Depression ORDepressive disorder* OR Anxiety OR Anxiety disorder* OR Psychosis OR Psychotic disorder* OR mental disease 2 Clinical practice guideline* OR Clinical guideline* OR Practice guideline* OR Prescribing guideline* OR Prescribing recommendation* OR Treatment guideline* OR practice guideline 3 Clinical practice* OR Practice pattern* OR Guideline adherence* OR Guideline concordance* OR Prescribing pattern* OR Prescribing trend* OR clinical practice 4 Prescri* OR Psychotrop* OR Antidepressant* OR Anti-depressant* OR Antipsychotic* OR Anti-psychotic* OR Anxiolytic* OR Mood stabili?er* OR antidepressant agent OR neuroleptic agent OR anxiolytic agent OR mood stabilizer 5 1 AND 2 AND 3 AND 4 6 Exclude MEDLINE from 5 CINAHL search: 1 Mental health* OR Mental illness* OR Mental disorder* OR Depression OR Depressive disorder* OR Anxiety OR Anxiety disorder* OR Psychosis OR Psychotic disorder* OR Mental Disorders 2 Clinical practice guideline* OR Clinical guideline* OR Practice guideline* OR Prescribing guideline* OR Prescribing recommendation* OR Treatment guideline* OR Practice Guidelines 3 Clinical practice* OR Practice pattern* OR Guideline adherence* OR Guideline concordance* OR Prescribing pattern* OR Prescribing trend* OR Guideline Adherence OR Prescribing Patterns 4 Prescri* OR Psychotrop* OR Antidepressant* OR Anti-depressant* OR Antipsychotic* OR Anti-psychotic* OR Anxiolytic* OR Mood stabili?er* OR Psychotropic Drugs 5 1 AND 2 AND 3 AND 4 References Advisory Council on the Misuse of Drugs, 2000. Reducing Drug Related Deaths: A Report By the Advisory Council On the Misuse of Drugs. Stationery Office, London.

8

Psychiatry Research xxx (xxxx) xxxx

T. Nguyen, et al.

Psychiatrists, Leicester (UK). National Institute for Health Care Excellence, 2014. Developing NICE Guidelines: The Manual. Manchester. National Institute for Clinical Excellence. O’Sullivan, K., Boland, F., Reulbach, U., Motterlini, N., Kelly, D., Bennett, K., Fahey, T., 2015. Antidepressant prescribing in Irish children: secular trends and international comparison in the context of a safety warning. BMC Pediatr. 15, 119 -119. Perera, A., Gupta, P., Samuel, R., Berg, B., 2007. A survey of anti-depressant prescribing practice and the provision of psychological therapies in a South London Camhs from 2003 to 2006. Child. Adolesc. Ment. Health 12 (2), 70–72. Ricken, R., Wiethoff, K., Reinhold, T., Schietsch, K., Stamm, T., Kiermeir, J., Neu, P., Heinz, A., Bauer, M., Adli, M., 2011. Algorithm-guided treatment of depression reduces treatment costs–results from the randomized controlled German Algorithm Project (GAPII). J. Affect. Disord. 134 (1–3), 249–256. Robertson, J., 2000. New British guidelines on the clinical management of drug misuse and drug dependence. Addiction 95 (3), 325. Scottish Intercollegiate Guidelines Network,Harbour, R.T., Forsyth, L., 2008. SIGN 50: A guideline Developer's Handbook. Scottish Intercollegiate Guidelines Network. Skaer, T.L., Sclar, D.A., Robison, L.M., 2009. Trends in prescriptions for antidepressant pharmacotherapy among US children and adolescents diagnosed with depression, 1990 through 2001: an assessment of accordance with treatment recommendations from the American Academy of Child and Adolescent Psychiatry. Clin. Ther. 31 (6), 1478–1487. St Patrick's University Hospital, 2011. Prescribing and monitoring of antipsychotic medication, including high dose antipsychotic medication. Policy No. CLIN 0007. Strang, J., 1999. Updated Guidance on Drug Misusers Focuses on Primary Care. Guidelines in Practice 2. Strang, J., Manning, V., Mayet, S., Ridge, G., Best, D., Sheridan, J., 2007. Does prescribing for opiate addiction change after national guidelines? Methadone and buprenorphine prescribing to opiate addicts by general practitioners and hospital doctors in England, 1995-2005. Addiction 102 (5), 761–770. The Management of Posttraumatic Stress Disorder Work Group, 2017. VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. The Department of Veterans Affairs and th Department of Defense, Washington, DC. The Management of Posttraumatic Stress Disorder Working Group, 2004. VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder. The Department of Veterans Affairs and the Department of Defense, Washingdon, DC. Vasile, R.G., Bruce, S.E., Goisman, R.M., Pagano, M., Keller, M.B., 2005. Results of a naturalistic longitudinal study of benzodiazepine and SSRI use in the treatment of generalized anxiety disorder and social phobia. Depression Anxiety 22 (2), 59–67. Vasudev, K., Mead, A., 2010. Use of valproate in women of childbearing potential: preand post-NICE bipolar guidelines. Arch. Womens Ment. Health 13 (4), 371–372. Vries, Y., Jonge, P., Kalverdijk, L., Bos, J., Schuiling-Veninga, C., Hak, E., 2016. Poor guideline adherence in the initiation of antidepressant treatment in children and adolescents in the Netherlands: choice of antidepressant and dose. Eur. Child. Adolesc. Psychiatry 25 (11), 1161–1170. Weinmann, S., Koesters, M., Becker, T., 2007. Effects of implementation of psychiatric guidelines on provider performance and patient outcome: systematic review. Acta Psychiatr. Scand. 115 (6), 420–433. Wijlaars, L.P.M.M., Nazareth, I., Petersen, I., 2012. Trends in depression and antidepressant prescribing in children and adolescents: a cohort study in the health improvement network (THIN). PLoS ONE [Electronic Resource] 7 (3), e33181. Wolraich, M., Brown, L., Brown, R.T., DuPaul, G., Earls, M., Feldman, H.M., Ganiats, T.G., Kaplanek, B., Meyer, B., Perrin, J., Pierce, K., Reiff, M., Stein, M.T., Visser, S., 2011. ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics 128 (5), 1007–1022. Wright, N.M., Roberts, A.J., Allgar, V.L., Tompkins, C.N., Greenwood, D.C., Laurence, G., 2004. Impact of the CSM advice on thioridazine on general practitioner prescribing behaviour in LEEDS: time series analysis. British Journal of General Practice 54 (502), 370–373.

186, 171–177. Okechukwu, K., 2019. Personal email communication, in: Tony Nguyen (Ed.). Lai, I.C., Wang, M.T., Wu, B.J., Wu, H.H., Lian, P.W., 2011. The use of benzodiazepine monotherapy for major depression before and after implementation of guidelines for benzodiazepine use. J. Clin. Pharm. Therap. 36 (5), 577–584. Landelijke Stuurgroep Multidisciplinaire Richtlijnontwikkeling in de GGZ, 2008. Multidisciplinaire Richtlijn Persoonlijkheidsstoornissen. Richtlijn voor De Diagnostiek En Behandeling Van Volwassen Patiënten Met Een persoonlijkheidsstoornis. [Dutch Multidisciplinary Guideline For the Diagnosis and Treatment of Personality Disorders]. Utrecht, The Netherlands. Landelijke Stuurgroep Multidisciplinaire Richtlijnontwikkeling in de GGZ, 2009. Multidisciplinaire richtlijn Addendum Depressie bij Jeugd [Dutch multidisciplinary guideline addendum for depression in youth]. Leucht, S., Cipriani, A., Spineli, L., Mavridis, D., Orey, D., Richter, F., Samara, M., Barbui, C., Engel, R.R., Geddes, J.R., Kissling, W., Stapf, M.P., Lassig, B., Salanti, G., Davis, J.M., 2013. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 382 (9896), 951–962. Lieb, K., Völlm, B., Rücker, G., Timmer, A., Stoffers, J.M., 2010. Pharmacotherapy for borderline personality disorder: cochrane systematic review of randomised trials. Br. J. Psychiatry 196 (1), 4–12. Linden, M., Schotte, K., 2007. A randomized controlled clinical trial comparing “guideline exposed” and “guideline naive” physicians in respect to dosage selection and treatment outcome with doxepin in depressive disorders. Pharmacopsychiatry 40 (2), 77–81. Lugtenberg, M., Burgers, J.S., Westert, G.P., 2009. Effects of evidence-based clinical practice guidelines on quality of care: a systematic review. Qual. Saf. Health Care 18 (5), 385–392. Lyall, L.M., Penades, N., Smith, D.J., 2019. Changes in prescribing for bipolar disorder between 2009 and 2016: national-level data linkage study in Scotland. Br. J. Psychiatry 215 (1), 415–421. Mago, R., 2016. Adverse effects of psychotropic medications: a call to action. Psychiatric Clin. N. Am. 39 (3), 361–373. Martin-Blanco, A., Ancochea, A., Soler, J., Elices, M., Carmona, C., Pascual, J.C., 2017. Changes over the last 15 years in the psychopharmacological management of persons with borderline personality disorder. Acta Psychiatr. Scand. 136 (3), 323–331. Murad, M.H., 2017. Clinical practice guidelines: a primer on development and dissemination. Mayo Clin. Proc. 92 (3), 423–433. National Collaborating Centre for Mental Health, 2009. Borderline Personality Disorder: Treatment and Management. British Psychological Society. National Guideline Clearinghouse, 2018. NGC and NQMC inclusion criteria. Agency for Healthcare Research and Quality, Rockville, Maryland. National Health Medical Research Council, 1999. A Guide to the development, Implementation and Evaluation of Clinical Practice Guidelines. NHMRC, Canberra. National Health Medical Research Council, 2012. Clinical Practice Guideline for the Management of Borderline Personality Disorder. National Health and Medical Research Council, Melbourne. National Health Medical Research Council, 2016. 2016 NHMRC standards for guidelines. National Heart Lung and Blood Institute, 2019. Study Quality Assessment Tools. National Institutes of Health, US Department of Health and Human Services. Available from: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools. Accessed April 2019. National Institute for Clinical Excellence, 2004. Depression: management of depression in primary and secondary care (CG23), London. National Institute for Health and Care Excellence, 2005. Depression in children and young people: identification and management (CG28). National Institute for Health and Care Excellence, 2009. Depression in adults: recognition and management (CG90). National Institute for Health and Care Excellence, 2019. Personal email communication, in: Tony Nguyen (Ed.). National Institute for Health and Clinical Excellence, 2006. Bipolar disorder: the management of bipolar disorder in adults, children and adolescents. Primary and Secondary Care. The British Psychological Society & The Royal College of

9