Prescribing in Personality Disorder

Dr.Sanjeevan Somasunderam

Consultant Psychiatrist,

MAP East team,

Croydon

CONTENT

• NICE Guidelines

• The Dilemma in prescribing mood stabilisers/antipsychotics

• Relevant research papers and findings/problems with research

• Polypharmacy/Washout

• Summary and Conclusions

NICE GUIDELINES

• Drug treatment should not be used specifically for borderline personality disorder or for the individual symptoms or behaviour associated with the disorder (for example, repeated self-harm, marked emotional instability, risk-taking behaviour and transient psychotic symptoms)

• Too unequivocal/dogmatic

• No definitive/robust evidence either way

• Does not reflect clinical practice in secondary care though there is variation in clinical practice

• May encourage a lack of curiosity of potential co-morbidities in staff

• Emerging evidence of underdiagnosed ADHD and Bipolar Affective Disorder(type 2,and sub-syndromal) within E.U.P.D patient group

The Dilemma in prescribing mood stabilisers/anti-psychotics

• Issues of risk/benefit considering risk of O.D and toxicity of medication

• Influence of the availability of timely psychological therapies(effect on prescribing)

• Patient pressure

• Initiating a cycle of medication trials and potential to lead to polypharmacy/ ‘irrational’ polypharmacy

• Lack of a standardised clinical approach

• Diagnostic counter-transference and effect on prescribing patterns

Relevant research papers and findings/problems with research

• Medication prescribed to people with personality disorder: The influence of patient factors and treatment setting. Acta Psychiatrica Scandinavica 2011 Crawford et al

• Polypharmacy or medication washout: An old tool revisited Neuropsychiatric Disease and treatment. 2011 Hoffman et al

• Are mood stabilisers helpful in treatment of borderline personality disorder? BMJ 2014 Crawford et al

• Depression and borderline personality disorder. MJA 2012 Beatson et al

• Antipsychotics,Antidepressants,Anticonvulsants and placebo on Symptom dimension of borderline personality Disorder. Journal of clinical psychopharmacology Oct 2011 Vita et al * Meta-Analysis Of Randomized Controlled and Open-Label Trials

• Comparison of Low and Moderate dosages of Extended-release Quetiapine in Borderline Personality Disorder: A Randomised,Double-Blind,Placebo-Controlled Trial. The American Journal of Psychiatry 2014: Black et al *

Patient factors and treatment setting

• Potential for polypharmacy is greater(in EUPD)

• Clinicians may fail to recognise P.D and use treatment for Axis 1 condition that is not there

• When response is poor, increase doses/’irrational’ polypharmacy

• Service provider with the highest level of prescribing was the one that did not have a specialist unit(psychotherapy)

• In the univariate analysis, patients with anti-social personality disorder were less likely to receive psychotropic medications than other groups of P.D(despite high levels of Axis 1 disorders in this group)

• It has been argued that counter-transference involved by people with P.D is important in determining the treatment that people receive.

Polypharmacy or medication washout

• Washout as a clinical tool is rarely done today• ‘Rational’ vs ‘Irrational’ polypharmacy• Reasons for polypharmacy may be mutifactorial,increase availability of

medications targeting specific symptoms and receptors• Inadequacies in our current diagnostic nomenclature based as it is on

descriptive psychiatry• Question arises as to whether the risk of adding another medication is

less than the risk of washout• Can provide valuable information about which medications are actually

beneficial• Allow 5-7 half lives as a rule of thumb for clearance,?need for in-patient

washout• ‘Irrational’ polypharmacy when clinicians are afraid of changing the

status quo by altering a medication that maybe only partially effective

• ‘Rational’ polypharmacy: ‘mini-experiments’ drawing on good pharmacological decisions,avoid several benzo’s,several anti-psychotics

• Difficulty finding RCT’s on polypharmacy(expensive and driven by pharma)

• Low-rate of washout failure(suggests that they were not truly treatment resistive)

• Risks of polypharmacy appear greater than the risks associated with washout

Are mood stabilisers helpful in treatment of Borderline Personality Disorder? BMJ 2014

• Cochrane Systematic review 2009:results of randomised trials of mood stabilisers in Borderline P.D,small trials,short follow-up

• Diverse range of outcome measures were used,limiting the scope for meta-analysis

• Difficulty finding ‘pure’ E.U.P.D cases

• Study participants had less severe problems than those in secondary care

• Recommendations include,no routine use of mood stabilisers for BPD

• Possible potential,evidence from pragmatic trials among people using secondary care is lacking and no data on long term clinical and cost effectiveness exist

• Consider side-effect profile,drug interactions,previous Hx of adherence and self-harm using prescribed drugs and women of child bearing age

• Patients to be told of uncertain benefit,risks/’off-license’ use and will be discontinued after 3-6 months if Sx don’t improve

• A decision to stop meds may trigger feelings of abandonment,but this is not a sound basis for continuing treatments that are ineffective.

Depression and borderline personality disorder. MJA 2012 Beatson et al

• Major depressive Disorder(MDD) commonly co-exits with BPD

• MDD co-occurring with BPD does not respond as well to anti-depressant medication

• MDD is not a significant predictor of outcome for BPD,but BPD is a significant predictor of outcome for MDD

• One study ,BPD patients( twice as likely to receive anti-convulsants,x6 for mood stabilsers,x10 anti-psychotics and x2 anti-depressants cf MDD alone)

Antipsychotics,Anti-depressants,Anticonvulsants,and Placebo on the Symptom Dimensions of Borderline Personality Disorder-Vita 2011

• Sx Dimensions of 1)Affective Dysregulation 2)Impulsive-Behavioural Dyscontrol 3)Cognitive-perceptual Sx

• No previous quantitative review of open label studies was available and no attempt to compare the results from RCT’s and open-label trials.

• 3 separate sets of meta-analysis for 1)RCT’s 2)Open studies 3) RCT’s and open trials combined.Also analysed the effect of placebo on Sx dimensions.

• For Affective Dysregulation,highest efficacy with Anti-Convulsants,then less for anti-depressants and minimal,although significant for SGA’s

.

• Open-label studies showed yielded the same results for anti-convulsants and SGA’s.

• For Impulse-behavioural dyscontrol,RCT’s demonstrated the highest effect-size for anti-convulsants and a lower effect size for both FGA’s and SGA’s,no evidence of efficacy for anti-depressants.

• Open label-studies,anti-depressants were also shown to be effective(but very small number of open studies(n=3)

• For Cognitive-perceptual Sx dimension,in both RCT’s and open-trials,only anti-psychotics proved to be effective,the existing literature does not indicate any significant efficacy for anti-convulsants and anti-depressants

B: Impulsive-behavioural Dyscontrol

C:Cognitive-perceptual

• A more pronounced effect of anti-convulsants’ on affective dysregulation and should be considered 1st line for impulsive-behavioural dyscontrol and affective dysregulation

• Anti-psychotics appear to effective for the treatment of all core Sx of BPD,insufficient data on FGA’s vs SGA’s.

• Several limitations of the study,quality of the primary studies,huge heterogeneity of clinical features,treatment settings,outcome variables and assessment instruments adopted by the different studies.

• Relatively small and qualitatively heterogenous literature that could be included in the present analysis prevents definitive conclusions being drawn form the results and limits their interpretation.

• Meta-analysis on largest available database of RCT’s and open-label trials,when possible on a pooled data set of both RCT’s and open studies does demonstrate a positive effect of drug treatments on the core Sx of BPD.

• Also differences in efficacy between different drug classes on each Sx domain.

• Future research should use a more homogenous set of better described outcome measures and assessment instruments

• Further outcome measures other than symptomatological,that is,biological,neurocognitive,and psychosocial should be addressed,especially in long-term naturalistic studies.

• ?A SLaM group to look into this

SUMMARY• NICE Guidance not particularly helpful

• More helpful to consider Symptom Dimensions of E.U.P.D

• 1)Affective Dysregulation 2)Impulsive-behavioural dyscontrol 3)Cognitive-perceptual Symptoms

• Most interesting papers are from Antonio Vita and Black(Quetiapine) ,though it does highlight the ongoing problem with research in this group

• There is some evidence re:effectiveness of mood stabilisers in 1)Affective dysregulation and 2)Impulsive-behavioural dyscontrol

• Strategies of Washout to be considered when polypharmacy occurs

• Concepts of ‘rational’ polypharmacy and ‘irrational’ polypharmacy

• Awareness of potentially underdiagnosed disorders in this group(ADHD/F31)

• Awareness of Diagnostic Counter-transference,patient factors

• Prescribing of Mood stabilisers and anti-psychotics appears haphazard/not focussed.

• The need for a standardised approach from SLaM Consultants/teams

• Formation of Prescribing groups within the M.A.P C.A.G.