1. Yasir Hameed (ST4 Dual Training)
Jaap Hamelijnck (consultant psychiatrist)
Eastern Recovery Team
Northgate Hospital
12 November 2013

2. Overview
 Why we chose this case?
 Clinical details
 Congenital Adrenal Hyperplasia CAH
 The rare side effect (with literature review)
 CAH and psychiatric morbidity
 MCQs

3. NS
 33 year old white Caucasian female
 Driving instructor
 Living alone
 Congenital Adrenal Hyperplasia (CAH, 21 Hydroxylase
Deficiency)
 No previous contact with mental health services
 Referred by her GP in July 2010 due to mood swings,
lack of sleep and thought racing with suicidal ideas.

4. More information
 Bouts of depression since age of 18
 Was told about her genetic condition aged 15
 Only appreciated the full impact in her late 20s and
needed counselling
 Disturbed relationship with parents
 Thoughts of suicide and harming others (stabbing her
parents)
 Not psychotic
 No drugs or alcohol

5.  GP initiated Citalopram 20 mg, felt worse on
40 mg
 Temazepam 10-20 mg nocte
 Prednisolone 7 mg od
 Fludrocortisone 100 mcg od

6. Initial assessment
 Seen by psychiatrist in August 2010
 Talked about the diagnosis of the genetic
disorder and its impact on her mental
health
 Became reclusive, unable to speak to anyone
 Relationships difficulties
 Anxious and suspicious
 Thoughts of killing her parents

7.  Mood up and down. No middle ground. Since
teenager.
 Features of hypomania: overspending, easily irritable,
much more talkative, racing thoughts, easily distracted
, getting overly childish and giggling lasting about 2
weeks at a time. Depressed mood longer.
 Mood Disorder Questionnaire: 13 out of 13 for Q.1, and
considered these mood changes as having serious
effect on her life.

8. Presentation
Hypomanic Depressed
 Elated
 Lots of motivation
 Less need for sleep
 Impulsive
 Overconfident
 Last up to 3-4 weeks
 Low
 Lacks motivation
 Withdrawn
 Negative thoughts
 Feels useless
 Suicidal ideas
 Last 2-3 months

9. Anxiety
 Following a breakdown in 2010
 Very difficult to go out by herself
 Worries that something catastrophic might happen
 Unable to sleep, worrying that someone might break
into her home
 Great impact on her mood and her relations

10. Personal history
 Born in East Runton
 Normal delivery
 Delayed walking
 Main stream schools
 Care home assistant and driving instructor
 Bisexual

11. Bit more of history
 Social history
 Premorbid personality
 Medical history
 Drugs and alcohol
 Forensic history
 Family history

12. Diagnosis?

13. Diagnosis
 Bipolar affective disorder (current episode
mixed) F31.6

14. Formulation
 Predisposing factors:
 Genetics, family background, early life experience,
trauma, abuse, neglect.
 Precipitating factors:
 Triggers, relationship tensions, employment issues.
 Perpetuating factors:
 Avoidance, mistrust, unemployment, dependent on
parents.

15. Simplified representation of the early stages of bipolar disorder.
Elanjithara T E et al. APT 2011;17:283-291
©2011 by The Royal College of Psychiatrists

16. Progress
 Quetiapine gradually increased to 300 mg
XL preparation
 Good response
 Discharged in November 2010

17. Re-referred January 2011
 Low mood
 Given up work
 Now living with parents
 Quetiapine increased to 400 mg without
good effect

18. Psychiatrist review February 2011
 Short hypomanic spells lasting 1-2 weeks followed
by longer periods of depression
 Angry, anxious and easily frustrated
 Quetiapine switched to Olanzapine
 Mirtazapine started
 Very sedated on olanzapine, switched to Sodium
Valproate

19. August 2011 to March 2012
 Sodium valproate 600 mg daily
 Mirtazapine 45 mg nocte
 Good effect
 Referred to IAPT
 Discharged in March 2012

20. Re-referred by link worker July 2012
 Mood swings
 Medication review
 Prednisolone 7 mg od
 Fludrocortisone 100 mcg od
 Sodium Valproate 600 mg daily
 Mirtazapine 30 mg nocte

21. Consultant psychiatrist September
2012
 Significant mood swings
 Severe anxiety
 Clear hypomanic symptoms alternating with
depression
 Thoughts of planning her funeral but no
active suicidal plans

22. Discussion around lithium
 Endocrinologist opinion needed
 Fludrocortisone dose may need increase
 Monitoring level of renin
 Prednisolone role
 Lithium started in October 2012

23. October 2012-May 2013
 Good response to lithium even with low
levels
 Subsequent levels approached therapeutic
levels
 Offered CBT for Panic Disorder with
Agoraphobia and was very successful

24. CBT Assessment
 Situation: shopping with mum
 Thoughts: “here we go, people are attacking me”.
 Enhanced awareness: scanning the area, heart racing, body
is shaking
 Behaviours: scanning area for potential threats from
others, “I need to protect my mum and stay close”, keep
others at safe distance
 Catastrophic misinterpretation: “I’d die in the hands of
some idiot” (random attacks in public places)
 Safety behaviours: scan the area, get out, avoid.
 After: headaches, “fed up with myself”, what was the fuss
about

25. July 2013
 Mainly low mood with some brief elevations
 Agreed to introduce a second agent
 Lamotrigine commenced with 25 mg od
 Started to experience auditory and visual
hallucinations
 Never had them before
 “Weird but not frightening”

26. Current situation (Oct-Nov 2013)
 Lamotrigine stopped and lithium increased to gain
better therapeutic level
 Still on the low side. Frustrated. Want to get back to
work.
 Discussed adding Quetiapine or Topiramate
 Current medication: Lithium 1 g od (latest level 0.8 on
29.10.13), Mirtazapine 30 mg od. Prednisolone and
Fludrocortisone. Vitamin D3.

27. Discussion and literature
 CAH and psychiatry
 Lamotrigine and hallucination

28. Congenital Adrenal Hyperplasia (CAH)
 Autosomal recessive
 21 Hydroxylase deficiency is most common
 Incidence is 1:5000 to 1:15000 live birth
 The enzyme deficiency causes reduction in
end-products, accumulation of hormone
precursors & increased ACTH production

29. Dehydroeplandrosterone
(DHEA)
Cholesterol
Pregnenolone 17-hydroxypregnenolone
Progesterone 17-
hydroxyprogesterone
(17-OHP)
Androstenedione
Deoxycorticosterone 11-deoxycortisol Testosterone
Corticosterone Cortisol
Aldosterone
21-hydroxylase 21-hydroxylase

31. Symptoms
Male
 Enlarged penis
 Failure to regain birth weight
 Weight loss
 Dehydration
 Vomiting
 Precocious puberty
 Rapid growth during
childhood, but shorter than
average final height.
Female
 Ambiguous genitalia
 Failure to regain birth weight
 Weight loss
 Dehydration
 Vomiting
 Precocious puberty
 Rapid growth during
childhood, but shorter than
average final height.
 Infertility
 Irregular or absent
menstruation
 Masculine characteristics

32. Symptoms
Young woman with
excess hair growth
Baby girl with
ambiguous genitalia.

33. Treatment
 Glucocorticoids which suppress ACTH, are used to reduce
the levels of adrenal sex steroids in the blood
 Individuals with salt wasting CAH also require
mineralocorticoids and sodium chloride supplements
 Surgery on virilised females
 Growth monitoring to detect over and under treatment
 Counselling

34. Psychiatric manifestations of CAH
 According to Riepe et al., 71% of female CAH patients suffer
from psychosexual problems. Of these, only 17% undertook
routine psychiatric diagnosis and counseling.*
 Berenbaum et al. found that adult females with CAH as a
result of 21-hydroxylase (21-OH) deficiency had good
overall psychological adjustment, similar to that of the
control group. **
*Riepe FG, Krone N, Viemann M, Partsch CJ, Sippell WG. Management of congenital adrenal
hyperplasia: results of the ESPE Questionnaire. Horm Res 2002;58:196-205.
**Berenbaum SA, Korman Bryk K, Duck SC, Resnick SM. Psychological adjustment in children
and adults with congenital adrenal hyperplasia. J Pediatr 2004;144:741-6.

35.  However, specific problems, such as gender identity, sexual
orientation and sex-typed behavior, psychosexual function,
body images, psychiatric adjustment and quality of life,
have been evaluated and found to be associated with the
illness when using different assessment instruments.
 With regard to childhood psychiatric comorbidity, few
studies have revealed that intersex people have an
increased prevalence of mental disorders, except that some
individuals with CAH struggled to adjust to their
condition.

36. Male-type behaviours
 Studies in females suffering from CAH have documented a
higher than expected prevalence of male-typical traits and
behaviours, more male typical childhood play, show more
interest in male-typical activities and careers, and exhibit
more aggression than unaffected females.
 Most women with congenital adrenal hyperplasia have
good long term psychological outcome, with no dramatic
increase in psychological morbidity, good social
adjustment, and no deficit in self esteem
Morgan et al. Long term psychological outcome for women with congenital adrenal hyperplasia:
cross sectional survey. BMJ VOLUME 330 12 FEBRUARY 2005 bmj.com

37. Hallucination with Lamotrigine
Only one case report describing this in patients
without an underlying neurological disorder
“To our knowledge, this is the first report of
Lamotrigine-induced hallucinations in a subject
without neurological illness.”
Uher R, Jones HM. 2006. Hallucinations during lamotrigine
treatment of bipolar disorder. Am J Psychiatry, 163:749–50.

38. Psychiatric symptoms related to the use
of Lamotrigine: a review of the literature
Lamotrigine is generally well tolerated; however,
some psychiatric problems have been reported in
patients using the drug to treat mental disorders
(mainly bipolar) or epilepsy
The clinical features of these psychiatric
side effects are: affective switches, full acute
psychotic episodes, and hallucinations
Villari et al. Functional Neurology 2008; 23(3): 133-136

39. eHealthMe data
 On Oct, 19, 2013: 33,726 people reported to have side effects when taking
Lamotrigine. Among them, 275 people (0.82%) have Hallucinations.
 Time when people have Hallucinations: 40% less than one month after
starting Lamotrigine. 48% between 1-6 months, lower thereafter.
 Top conditions involved for these people :
1. Bipolar disorder (86 people, 31.27%)
2. Epilepsy (53 people, 19.27%)
3. Depression (47 people, 17.09%)
4. Drug use for unknown indication (19 people, 6.91%)
5. Anxiety (16 people, 5.82%)

40. Conclusions
 Role of CAH (the disorder itself and its treatment) in
her presentation
 Significance of the rare Lamotrigine reaction
 Future long term management
 Role of Multidisciplinary team

41. MCQ Select the single best option for each question stem
1. Age at onset of bipolar disorder:
a) has little prognostic relevance
b) is not a heritable trait
c) has been observed to be higher in more recent studies
d) is higher in women than men
e) has implications for clinical course.

42. MCQ Select the single best option for each question stem
1. Age at onset of bipolar disorder:
a) has little prognostic relevance
b) is not a heritable trait
c) has been observed to be higher in more recent studies
d) is higher in women than men
e) has implications for clinical course.

43.  2. Individuals with bipolar disorder:
a) rarely receive a diagnosis of unipolar depression
b) have longer episodes of mania than depression
c) commonly have psychiatric comorbidities
d) have fewer depressive episodes than those with unipolar
depression
e) show poorer prognosis if they have predominantly manic
episodes

44.  2. Individuals with bipolar disorder:
a) rarely receive a diagnosis of unipolar depression
b) have longer episodes of mania than depression
c) commonly have psychiatric comorbidities
d) have fewer depressive episodes than those with unipolar
depression
e) show poorer prognosis if they have predominantly manic
episodes

45. 3. When compared with bipolar I disorder,
bipolar II disorder:
a) is associated with better inter-episode functioning
b) is similar and frequently develops into bipolar I
disorder
c) is associated with fewer affective episodes overall
d) has a less chronic course
e) has a significantly higher age at onset

46. 3. When compared with bipolar I disorder,
bipolar II disorder:
a) is associated with better inter-episode functioning
b) is similar and frequently develops into bipolar I
disorder
c) is associated with fewer affective episodes overall
d) has a less chronic course
e) has a significantly higher age at onset

47. 4. Regarding the treatment of bipolar disorder:
a) delays in initiating treatment are rare
b) the vast majority of patients respond to lithium or an
anticonvulsant treatment when in a manic phase
c) quetiapine leads to remission in over 50% of patients
in the depressive phase
d) there are a number of well-tolerated treatments that
are effective in all phases of the illness
e) the majority of patients are maintained on
monotherapies.

48. 4. Regarding the treatment of bipolar disorder:
a) delays in initiating treatment are rare
b) the vast majority of patients respond to lithium or an
anticonvulsant treatment when in a manic phase
c) quetiapine leads to remission in over 50% of patients
in the depressive phase
d) there are a number of well-tolerated treatments that
are effective in all phases of the illness
e) the majority of patients are maintained on
monotherapies.

49. 5. Common comorbid conditions include:
a) anxiety disorders in 5% of patients
b) rheumatoid arthritis
c) thyroid disease
d) tension headache
e) unipolar depression.

50. 5. Common comorbid conditions include:
a) anxiety disorders in 5% of patients
b) rheumatoid arthritis
c) thyroid disease
d) tension headache
e) unipolar depression.

51. Thanks