1) The document provides an overview of personality disorder and depression, including discussing borderline personality disorder as an example. It outlines current principles for managing personality disorders and depression. 2) For borderline personality disorder specifically, it discusses the diagnostic criteria, biological and psychosocial risk factors, and developmental model. It recommends psychological treatments like dialectical behavior therapy and describes principles for managing BPD as a GP. 3) For depression, it discusses the biology and psychology, principles of prescribing antidepressants according to severity and duration, and future treatment approaches targeting different systems like the glutaminergic and immune systems.

1. @BMJMasterclass
#GPGeneral
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2. GP
General
Update
Personality Disorder and Depression
Dr. Nick Stafford
Consultant Psychiatrist, Black Country Partnership NHS FT

3. #GPGeneral
Declaration of interests
• Trustee for national Mind (NAMH charity), London
• Specialist advisor Care Quality Commission
• Regional representative Royal College of Psychiatrists (West Midlands)
• Royal College of Psychiatrists, General Adult Faculty Exec. Comm. member
• Author:
– Lithium for bipolar disorder, a guide for patients
– Medication for bipolar disorder, a complete guide for patients
• Editor: Bipolar Disorder for Dummies, Wiley USA
• No pharmaceutical fees, sponsorship, educational funds >5 years
• No shares in pharma (nor in immediate family)

4. #GPGeneral
Learning Objectives
• Managing personality disorder
• Borderline personality disorder as an example
• Current principles
• Depression
• Current principles of management
• The future psychopharmacology of depression

5. #GPGeneral
PERSONALITY DISORDER,
BORDERLINE (EUPD)

6. #GPGeneral
General criteria PD summary
• Difficulty relating to themselves, others, the world
• Enduring patterns
– Inner experience (think, feel, relate, impulse control)
– Inflexible and pervasive: personally & socially
– Functioning, distress, impairment
– Stable, long duration, since adolescence/childhood
– Not accounted for by other diagnoses (e.g. LD/ID)
– Not caused by a substance or alcohol (but this maybe comorbid)

7. #GPGeneral
Personality disorder classification
Disorders
• Paranoid
• Schizoid
• Schizotypal
• Antisocial
• Borderline
• Histrionic
• Narcissistic
• Avoidant
• Dependent
• Obsessive-compulsive
Cluster
• A: Odd, bizarre, eccentric
• B: Dramatic, erratic
• C: Anxious, fearful
Severity 5 point rating
• 0 = no PD
• 1 = personality difficulty
• 2 = simple PD
• 3 = complex PD
• 4 = severe (& enduring) PDDSM-5
Tyrer & Johnson 1996

8. #GPGeneral
Borderline (specific) DSM-5 diagnostic
criteria
FIVE (or more) of the following:
• Avoid real or imagined abandonment
• Unstable and intense interpersonal relationships, extremes of
idealization and devaluation
• Identity disturbance
• Impulsivity
• Recurrent suicidal behaviour
• Affective instability
• Chronic feelings of emptiness
• Inappropriate, intense anger or difficulty controlling anger
• Transient, stress-related paranoid ideation or dissociation

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PD Assessment
• Validated assessment tool (specialist tools):
– IPDE (International Personality Disorder Evaluation)
– MMPI (Minnesota Multiphasic Personality Inventory)
• DSM-5 / ICD-10 diagnostic criteria
– General criteria
– Specific BPD criteria

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Specific
environmental
influences
Biological
vulnerabilities
Individual
Biosocial model Linehan 1993
BPD

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Biology of BPD
• Brain structure & function
– Area volumes & functions (frontal, temporal, executive function)
– Connectivity studies, Corticolimbic system, Autonomic functioning
– Impaired recognition of emotional faces
• Neurotransmitters
– Serotonin, dopamine, vasopressin, acetylcholine, noradrenaline, GABA
• Genetics
– TPH2. 5HTR2A and 5HTR2C. Dopamine. ACh. NA. HPA.
• Epigenetics
– Oxytocin receptor. Trauma and methylation, downregulates receptor
expression (impaired self soothing)

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Psychosocial risk factors for BPD
BorderlinePersonality
Disorder
Family psychopathology
Disrupted attachment relationships
Invalidating environments
Child maltreatment & abuse
Sociocultural correlates of BPD

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Developmental model of BPD
Poor impulse control emerges early
Biological
vulnerabilities &
other impulse
disorders
Extreme emotional lability
Shaped and
maintained by
the caregiving
environment
Reciprocal reinforcing transactions
Biological
vulnerabilities
and
environmental
risk processes
potentiate
emotion
dysregulation
Maladaptive coping strategies
Constellation of
these by mid-
adolescence
Relationships
Evocative
effects on
interpersonal
relationships
and social
functioning and
interference with
healthy
emotional
development

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The course of PDsStress
Relationships
with partners,
parents,
dependents,
care givers
Socialalienation At a time of
their greatest
need
Excludedfromhelp
By rejecting
help without
realizing they
are doing so
Clinicalskills
Paramount in
managing the
disorder.
Do not express
the view they
are rejecting
services or
manipulating
professionals.
Remission over time

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Psychological treatments BPD
• Dialectical behaviour therapy (DBT)
• Transference-focused psychotherapy (TFP)
• Cognitive behavioural therapy (CBT)
• Cognitive analytic therapy (CAT)
• Psychodynamic-interpersonal, therapeutic
communities (TC)

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Modules of DBT
Core
mindfulness
Distress
tolerance
Emotion
regulation
Interpersonal
effectiveness

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Function of DBT modules
•Identify and label emotions
•Identify obstacles to changing emotions
•Reduce vulnerability to the emotional mind
•Increase positive emotional events
•Increase mindfulness to current emotions

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Golden
rules
managing
PDs in GP
1/5 seen
Relationship
Medication
Therapy

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Golden rules for PDs in GP -
Relationship
• Manage the relationship
– Have a good rapport but keep good boundaries
– No boundaries in the relationship and the patient will be harmed
– Manage expectations: more is not better, often its worse
– Don’t be drawn in by your better nature (GP’s personality issues)
– Such as a need to satisfy your own narcissism
– EUPDs idealize you and split you by comparing you colleagues
• Consider the patient’s family relationships & occupation
– Are child protection services necessary?
– Do they have access to vulnerable people in their occupation,
OH involvement?

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Golden rules for PDs in GP –
Medication (1)
• Psychotropic medication does not alter the PD in the long term
• Sedative medication helps only in the short term
• SSRIs treat comorbid depression but little evidence
• Mood stabilizers may reduce impulsivity, anger and stabilize affect
• Lithium is licensed for the control of aggressive behaviour & DSH
• Opioid antagonist naltrexone may reduce DSH & dissociative
symptoms
• Dependence is common and doses are then increased, and so on…
– Ratchet prescribing patterns common
– Benzodiazepines and APs can be difficult to stop if not managed
• Manage the medication, like you manage the relationship

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Golden rules for PDs GP –
Antipsychotics (2)
• Open studies show first and second generation antipsychotics
benefit a wide range of PD symptoms
• RCTs however show only modest at best (if any) benefit
• In RCTs olanzapine appears to most robust (but still modest)
• Clozapine (open studies) reduces aggression & DSH, reduce
admission
– Clozapine reduces aggression in schizophrenia
– Most responsive symptoms:
• Affect dysregulation, Impulsivity, Cognitive-perceptual symptoms
– Risks and complications of clozapine

22. #GPGeneral
Medication (3)
I. Do not treat the BPD (this is for psychological treatment)
1. Do not use mood stabilizers for affect lability & impulsivity
2. Do not use antipsychotics for hallucinations
II. Treat the comorbid condition of BPD
1. Antidepressants for moderate to severe depression
2. Review AD as you would in other cases
3. Insomnia – short term (no more than 1-2 weeks) Z-drugs
4. Distress – short term (no more than 1-2 weeks) benzodiazepines
III. Non-licensed prescribing
1. Discuss with or refer to specialist

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Golden rules for PDs in GP - Therapy
• Psychological treatments are well established – refer
• If a patient doesn’t engage in psychological therapy
– Don’t engage in intensive GP follow up as a substitute
– Don’t substitute therapy with medication
– Consider them pre-contemplative (as you would with
alcoholism/substances)
– Use motivational interviewing techniques

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Depression & BPD – principles of
treatment
• Involving families and carers
• Comorbid – SM, ASD, mild LD, psychosocial
• Assessing needs
• Access to health services
• Supporting services (3rd sector)
• Developing relationships
• Managing self harm & suicide
• Managing ending and transitions

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Needs, Wellness, Recovery
• The dimensions of the
wellness wheel can be
useful to identify areas of
stress and need
• And areas of strength
• It is a useful holistic
multidimensional
management tool

26. #GPGeneral
BPD – Online resources (for patients &
carers)
• UK
– https://www.rcpsych.ac.uk/expertadvice/problemsdisorders/personalitydisorder.a
spx
– https://www.rethink.org/resources/b/borderline-personality-disorder-bpd-factsheet
– https://www.mind.org.uk/media/22544706/bpd-2018-downloadable-pdf.pdf
– http://personalitydisorder.org.uk
• USA:
– http://dbtselfhelp.com
– https://www.nimh.nih.gov/health/topics/borderline-personality-
disorder/index.shtml
– http://www.bpddemystified.com
– https://www.behavioraltech.org
– https://afsp.org

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DEPRESSION

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Borderline / Bipolar / Depression ???
• Differentiating between them
• Screen all depressed patients for elevated mood
• Point 1 – Family history of bipolar
• Point 2 – Duration of elevated mood in bipolar /
emotional instability
• Point 3 – Response to rejection and chaotic relationships
• Point 4 – Chronic emptiness in EUPD / Low self-esteem
in bipolar
• Ultimately the psychiatrist should make the diagnosis

29. #GPGeneral
Biology of depression
Serotonin
transporter gene
(5-HTTLR)
Genetics and
epigenetics
HPA - axis
Inflammation
Oxidative stress
CLOCK genes

30. #GPGeneral
Psychology of depression
• Cognitive approach (Beck & CBT)
• Behaviorist theory (Operant conditioning “A B C”)
• Psychodynamic / psychoanalytic theory (Freud)
• Seligman (Learned helplessness)
• Humanist theory (Maslow’s hierarchy of need)

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General issues in GP
• Overdiagnosis may be more common than underdiagnosis
• The more you see the patient, the greater the diagnostic accuracy
• Physical symptoms are often the presenting symptom of depression
• Prevalence in men = women, but men less likely to present
• Anxiety is the most common comorbidity
• Antidepressant prescribing has doubled in the last decade

32. #GPGeneral
Basic principles of prescribing in
depression (effectiveness)
• Discuss choice of drugs and availability of non-drug treatments
• Prescribe an effective dose (titrate promptly)
• Discuss likely outcomes (moderate to severe depression), define
Response:
– Without AD: 20-40% people on placebo improved within 6-8 weeks
– With AD: 40-60% people on AD improved within 6-8 weeks
– Alternatively: 20% recover with no Tx; 30% respond to placebo; 50%
respond to AD
– NNT: AD/nil Tx NNT = 3; AD/placebo NNT = 5

33. #GPGeneral
Basic principles of prescribing in
depression (maintenance)
• Single depressive episode: continue for 6-9 months
• Recurrent depression (RDD) / Treatment resistant depression: 2+ years
• Withdraw AD gradually, inform of discontinuation syndrome
• Prevention of relapse in RDD:
– Without AD:
50% of people on maintenance placebo relapsed within 1-2 years
– With AD:
23% of people on maintenance AD relapsed within 1-2 years

34. #GPGeneral
NICE
• Recent onset mild depression, do not use AD
– 1st line: active monitoring, guided self-help, CBT, physical
exercise
• AD recommended for moderate to severe depression & dysthymia
• Selection of AD: generic SSRI
• Treatment Resistance Depression (TRD):
– Augmentation (lithium, low dose AP, second antidepressant)
– Maintenance period at least 2 years
• ECT supported in TRD & severe depression
NICE 2017

35. #GPGeneral
Antidepressant efficacy
• The greater the severity of depression, the more efficacious ADs
• AD not effective in mild depression
• Avoid Citalopram:
– QTc problems esp. with augmentation
– Less tolerated in children (fluoxetine preferred)
• Most efficacious (head to head studies)
– Agomelatine, Amitriptyline, Escitalopram, Mirtazapine, Paroxetine,
Sertraline, Venlafaxine
• Most tolerated
– Agomelatine, Fluoxetine
• Reduced clinical benefits over last 30 years. HAM-D-21, HAM-D-17, HAM-
D-6. Trial length ><6/52.
Cipriani et al. 2014, 2018

36. #GPGeneral
Onset of action of AD
• Myth: 2-4 weeks
• Pattern of rate of improvement:
– Highest during weeks 1-2
– Lowest during weeks 4-6
– Statistical AD/placebo separation occurs
• In single trials between 2-4 weeks
• In meta-analyses between 1-2 weeks
• Patient notices improvement later than carer
• If no improvement after 3-4 weeks, change AD

37. #GPGeneral
SideeffectsofADs

38. #GPGeneral
Suicidality
• All patients should be warned and advised
• All AD implicated
• Early weeks of treatment
• When AD is stopped
• Particularly in adolescents and young adults
• Possible: increase in suicide in young women?
• ADs are switched in those aged >75 years
• Appropriate risk assessment
• Absolute risk of DSH / suicide is small
• Overall the use of AD greatly reduce suicidality (? Except
for young women)
Larsson 2017

39. #GPGeneral
Treatment Resistant Depression 1st line
• Augmentation strategies:
– Lithium
– Olanzapine plus Fluoxetine combination (OFC)
– Low dose AP:
• Quetiapine
• Aripiprazole
– SSRI plus buproprion (NA-DA reuptake inhibitor)
– SSRI or venlafaxine plus mirtazapine or mianserin
(tetracyclic)

40. #GPGeneral
TRD 2nd line augmentation strategies
• Add lamotrigine
• SSRI plus buspirone (5HT1A agonist)
• High dose venlafaxine
• ECT
• T3 (tri-iodothyronine)
• Low dose risperidone
• Add ketamine / intranasal esketamine (specialist and not
available widely in secondary care as yet)

41. #GPGeneral
The future systems
Glutaminergic
(NMDA)
Cholinergic Melatonergic HPA-axis
Immune
system
Oxidative
stress
Nitrosative
stress
CLOCK
genes.
GSK3β

42. #GPGeneral
The future systems
Ketamine,
Memantine,
Nitrous oxide
Cholinergic Melatonergic HPA-axis
Immune
system
Oxidative
stress
Nitrosative
stress
CLOCK
genes.
GSK3β

43. #GPGeneral
The future systems
Glutaminergic
(NMDA)
Scopolomine,
Biperiden
Melatonergic HPA-axis
Immune
system
Oxidative
stress
Nitrosative
stress
CLOCK
genes.
GSK3β

44. #GPGeneral
The future systems
Glutaminergic
(NMDA)
Cholinergic
Agomelatine
? pipeline
HPA-axis
Immune
system
Oxidative
stress
Nitrosative
stress
CLOCK
genes.
GSK3β

45. #GPGeneral
The future systems
Glutaminergic
(NMDA)
Cholinergic Melatonergic
Ketoconazole,
Mifepristone,
Pregnenalone
Immune
system
Oxidative
stress
Nitrosative
stress
CLOCK
genes. GSK3β

46. #GPGeneral
The future systems
Glutaminergic
(NMDA)
Cholinergic Melatonergic HPA-axis
Inteferon,
Infliximab
Oxidative
stress
Nitrosative
stress
CLOCK
genes.
GSK3β

47. #GPGeneral
The future systems
Glutaminergic
(NMDA)
Cholinergic Melatonergic HPA-axis
Immune
system
N-acetyl
cysteine,
O3FA
Nitrosative
stress
CLOCK
genes.
GSK3β

48. #GPGeneral
The future systems
Glutaminergic
(NMDA)
Cholinergic Melatonergic HPA-axis
Immune
system
Oxidative
stress
Smoking,
valproate
CLOCK
genes.
GSK3β

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The future systems
Glutaminergic
(NMDA)
Cholinergic Melatonergic HPA-axis
Immune
system
Oxidative
stress
Nitrosative
stress
Lithium

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Interactive 1
Which of the following antidepressants are known through
meta-analyses to have the highest effect size, compared to
all antidepressants? ‘choose 4 answers’
1. Citalopram
2. Escitalopram (CORRECT)
3. Agomelatine (CORRECT)
4. Fluoxetine
5. Mirtazapine (CORRECT)
6. Amitriptyline (CORRECT)

51. #GPGeneral
Interactive 2
The following medications are licensed for the treatment of
personality disorder (select one answer):
1. Lithium
2. Chlorpromazine
3. Naltrexone
4. Valproate
5. Lamotrigine
6. Fluoxetine
7. No drugs are licensed in the UK for PDs (CORRECT)

52. #GPGeneral
Interactive 3
When prescribing lithium it is important to warn the patient
that for the first few weeks they may experience an
increased desire to self-harm or suicidal thoughts?
1. True
2. False (CORRECT)

53. GP
General
Update
Thank you
Dr. Nick Stafford
Consultant Psychiatrist, Black Country Partnership NHS FT

54. @BMJMasterclass
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@BMJMasterclass
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