Bipolar
&
Bipolar Spectrum
Practical Clinical tips for the GP
Dr Michael Piperoglou
Private Psychiatric Consultant
Epworth Clinic Camberwell
History
• Ancient Greek clinicians described
– both euphoria and psychosis associated with manic states
– despair and suicidal inclinations with melancholic states.
• In 19th Century – Kraepelin made distinction between manic
depressive insanity and schizophrenia.
• Kraepelin found that
– manic depressive psychosis had good outcome
as compared to
– schizophrenia with often poor outcome.
• 1960 – Angst & Perris first used the term bipolar disorder.
–
This moved the depression spectrum away from psychosis.
Misdiagnosis: Is it bipolar depression?
Unrecognised bipolar disorder is a frequent contributor
to apparent treatment-resistant depression:
• Depression is the predominant mood state in bipolar disorder.
• Unipolar depression is the most common misdiagnosis.
• Prevalence of bipolar disorder in ‘treatment resistant’ depression
has been estimated at up to 80%.
• Diagnosis is often delayed for many years.
Misdiagnosis: Is it bipolar depression?
• Survey of 4,192 patients
diagnosed with bipolar
disorder;
• 69% were initially
misdiagnosed.
*More than one misdiagnosis possible.
Hirschfeld et al, 2003
Most common misdiagnoses of bipolar
disorder *
Unipolar depression
60%
Anxiety disorder
26%
Schizophrenia
18%
Borderline or antisocial
personality disorder
17%
Alcohol or substance
abuse/dependence
14%
Schizoaffective disorder
11%
12 Soft Bipolar signs
1. ≥ 4 episodes of MDD
2. 1st episode MDD < 25yr old
3. 1st degree relative with bipolar disorder
4. Hyperthymic personality
– extrovert, optimistic, little need for sleep
12 Soft Bipolar signs –(cont)
5.
Atypical depression- Hypersomnia, hyperphagia,
leaden paralysis, reactive mood to stresses
6.
Brief episodes ≤ 3months,
sudden onset, sudden offset
7.
Psychotic depression
8.
Post partum depression
12 Soft Bipolar signs –(cont)
9. Irritability, insomnia, agitation, hypomania with
antidepressants
10. ‘poop-out’ – loss of response to antidepressant (≤ 3months)
after good response
11. ≥3 antidepressants tried and failed
12. Seasonal mood shifts eg winter depression
Bipolar
Suggested treatment options
• Introduce a mood stabiliser before adding anti-depressant.
• If use antidepressant in Bipolar be careful of which
antidepressant, and only after mood stabiliser.
• Easiest mood stabiliser to use Epilim or Seroquel (although
both are sedative and increase weight).
• Lithium is not sedative, has less weight gain, but requires
blood monitoring.
Antidepressants in Bipolar Disorder
•
Start with MOOD-STABILISER
eg LITHIUM, EPILIM, ATYPICAL-SEROQUEL-XR, Zeldox,
Saphris, Zyprexa,
•
Add Antidepressant
1st Choice - SSRI, Zyban (or combo), Valdoxan
2nd Choice A – Cymbalta (low dose ≤60mg)
B - if insomnia – low dose AVANZA Sol-tab(≤15mg)
3rd Choice - if hypersomnia- MAOI-PARNATE, Nardil
•
AVOID PRISTIQ AND TRICYCLICS.
Piperoglou 2013
Suggested order of treatment options for
BIPOLAR DEPRESSION
Order
Treatment
Dose range
1st
ANTI-DEPRESSANT (LEXAPRO, Zoloft (SSRI’s),
Cymbalta) + EPILIM
Epilim – start low, go slow
200mg nocte – 1000mg
nocte
Dose range 700-3000mg
or
ANTI-DEPRESSANT as above
+ ATYPICAL (Seroquel XR, Saphris, Zeldox)
S-RX – 50mg-300mg nocte
Saphris-5-20mg nocte
Zel- 20-40 b.d. with food
A-2.5-5mg
------------------? Psych referral --------------------------------------------------------2nd
LITHIUM (low dosage) + ANTI-DEPRESSANT
LITHIUM (low dosage) + LAMOTRIGINE
3rd
LITHIUM or EPILIM + LAMOTRIGINE + ATYPICAL
4th
Lithium + MAOI
Piperoglou 2013
Bipolar Mixed States
Suggested treatment options
• Definition of Mixed states:
– Mood ↑or↓ + Energy/motor activity ↑or↓ + Thinking ↑or↓
• Suggested Treatment
MOOD STABILISER
- 1st Choice - EPILIM or LITHIUM
- 2nd Choice - TEGRETOL C.R.
+
ATYPICAL
- 1st Choice - Seroquel XR, Saphris or Zeldox
- 2nd Choice - Zyprexa
(NO ANTI-DEPRESSANT)
Piperoglou 2013
Lithium
•
Recommend low dose range :
0.3 – 0.6 mmol / l - Especially if used with DHA omega-3
•
Regular Investigations :
–
–
–
–
•
Serum Lithium
Thyroid function tests
Renal function tests
Serum Calcium
Precautions
– Dehydration – drink extra water
– Lithium toxicity when Li goes above 2.0 – rare on low dose
•
Side effects
– Metallic taste (suggest lozenge or gum)
– nausea, diarrhoea, tremor, polyuria, drowsiness, cognitive slowing
(much reduced on low dose).
Maintenance treatments of BIPOLAR
in my practice
• Bipolar II > Bipolar I
• Most common treatment
LITHIUM and/or EPILIM + SSRI Anti-depressant (Lexapro)
LITHIUM and/or EPILIM+LAMOTRIGINE
LITHIUM and/or EPILIM + Atypical (Seroquel XR, Saphris)+ Anti-depressant
•
Less Common
LITHIUM +/or EPILIM + ATYPICAL (Seroquel XR, Saphris Zeldox) + LAMOTRIGINE
TEGRETOL +/or LITHIUM +/- Anti-depressant +/- Atypical
• I encourage patients to also use DHA supplement (NeuroSpark)
• Psychotherapy/CBT considered only when patient is stabilised
Piperoglou 2013
References and Recommended Reading
Clinical Books:
Stahl, Stephen “Depression and Bipolar Disorder” Cambridge Medicine 2008
Vieta, Eduard “Managing the Rapid-Cycling Patient” Nowpharma 2007
Parker, Gordon (Ed) “Bipolar II Disorder”, 2nd edition, Cambridge Medicine 2012
Goodwin & Sachs “Bipolar Disorder” AstraZeneca 2007
Sphere – “Bipolar Disorder ALM” – SANE initiative
Patient Reading:
Phelps, Jim “Why am I still Depressed” McGraw-Hill 2006
Reference Papers:
Rao JS, Lee H-J, Rapoport SI and Bazinet RP, 2008; Molecular Psychiatry (2008) 13, 585–596
Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?
Masselin, Mireille et al, 2010; J Lipid Researh 51 1049- 56
Lithium modifies brain AA and DHA metabolism in rat LPS model of Neuroinflammation