New treatment options for use in bipolar mania Dr C Verster Dept Psychiatry Uuniversity of Stellenbosch

The Mind is its own place and in itself can make a Heaven a Hell, a Hell a Heaven John Milton

HIGH LOW Normal Mood

HIGH LOW Unipolar Depression (The Common Garden Variety)

HIGH LOW Bipolar (II) Disorder

HIGH LOW Bipolar (I) Disorder MANIA

Trying to describe bipolar disorder “The cogs of my mind are not all working together”

Case study ► 32yr old female patient (Pt AB) ► Going through divorce; 1 child (4yrs old) ► Working as secretary ► Known with diagnosis of Bipolar I Disorder ► On medication: Lithium 750mg at night ► Progressively less sleep x 2 weeks ► Irritability++

► On day of evaluation:  Grandiose  Refusing medication  Refusing to go to work  “Don’t need psychiatrist”  Praying to random people in the street  Giving away money ► Family “at wits’ end”  “This is the 3 rd such episode in 18 months”  “She will lose her child”  “Employer is fed-up”

What now? ► Admission  She refuses  Family unable to deal with her  Irresponsible behaviour (child’s safety)  Danger to self / reputation

Approach to Patient with acute manic relapse ► Admission ► Sedation ► Stabilization ► Prevention of relapse

Admission ► MHCA  Voluntary  Involuntary Pt AB: Needs admission ?Involuntary - certified

Sedation ► Benzodiazepines  Oral/Sublingual  IMI/IVI ► Antipsychotics (IMI)  Zuclopenthixol decanoate  Olanzapine IMI  Ziprasidone IMI  Haloperidol IMI  Clothiapine IMI Pt AB: Lorazepam IMI OR Olanzepine/ Ziprasidone IMI (NB Avoid IMI Benzo/Olanzepine combination)

Stabilization ► Behaviour / Sleep / Psychosis / Mood

What is a mood stabilizer?

► Bowden (2002): A drug that  benefits at least one primary aspect of bipolar illness  is effective in both acute and maintenance phases  does not worsen any aspect of the illness Traditional mood stabilizers: ► lithium, valproate, carbamazepine (recently: lamotrigine) ► Stahl 2010:  Includes atypical antipsychotics ► Antipsychotics always used in mania ► Atypicals also have effect on bipolar depression  (Antidepressants = mood destabilizers)

Generic Name Trade Name ManicMixedMaintenanceDepression Valproate Depakote(Epili m) X Carbamazepine extended release Equetro (Tegretol) X X Lamotrigine Lamictal (Lamictin) X Lithium X X AripiprazoleAbilify X X X ZiprasidoneGeodon X X RisperidoneRisperdal X X Asenapine Saphris (N/A) X X QuetiapineSeroquel X X Chlorpromazine Thorazine (Largactil) X OlanzapineZyprexa X X X Olanzapine/fluox etine combination Symbyax (N/A) X FDA Approved Bipolar Treatment Regimens FDA Approved Bipolar Treatment Regimens : Gutman DA, Nemeroff C. Atypical Antipsychotics in Bipolar Disorder. Medscape. Available at Accessed June 27,

2011 (Sachs et al; J Clin Psych) ► Category A evidence (Double blind placebo controlled trials; adequate sample) ► Efficacy for acute mania:  Lithium  Valproate  Carbamazepine  Olanzapine  Risperidone  Ziprasidone  Haloperidol  Quetiapine  Aripirazole  Paliperidone  Asenapine

Lithium ► Used since the 1950’s ► Effective mood stabilizer ► Narrow therapeutic range (Blood levels monitored) ► Toxicity  Acute  Chronic ► Thyroid ► Kidneys Pt AB: No use as sedative Why did she relapse? Why did she refuse medication? May still be of use in long term management

Anti Epileptics ► Carbamazepine / Valproate / Lamotrigine Pt AB: Limited efficacy in mania Side effect profile Pregnancy?

Antipsychotics ► Typicals  Haloperidol  Zuclopenthixol  Chlorpromazine ► Effective, but poor side-effect profile

Atypical antipsychotics

Why maintenance therapy? ► Prevention of relapse  ±80% relapse within 1 year without medication  ±20% relapse within 1 year with medication  In practice: ±50% relapse within 1 st year ► Because of poor treatment adherence

Cost of relapse ► Hospitalization (may be for weeks)  R per day  PMB ► Social & occupational consequences

Reason for poor adherence ► Poor psychoeducation  Lack of insight  Poor understanding of illness ► Side-effects ► Cost factors ► Social pressure/stigma ► Dosage interval / amount of tablets ► Religious / cultural factors ► Availability of medication ► Substance abuse ► Severity of illness

Stabilization/Maintenance Evide nce EPSProl.Sed.WeightGainTDNMSCVSRiskOtherCost Typicals ( ↑ potency) (++) ±+ Typicals ( ↓ potency) ± Amisulpiride Aripiprazole+ +/+ + (Akathisia)--±±±?-++++ Clozapine-± ±+++Agranulocyt.MiocarditisHypersaliv.++(+) Olanzapine Rash++ Quetiapine+± ±++++(+) Risperidone/Paliperidone ±± Ziprasidone++-±±±±++ Food effect ++++ Stahl, SM. The Prescriber’s Guide 3 rd ed; 2009

Pt AB ► Stabilize! ► Psychoeducation – also family! ► Lithium levels → discontinue or not? ► Monotherapy or combination? ► Illness profile  Sleeping pattern  Depressive episodes?  Cost factors

NB Bipolar Disorder should be managed by a psychiatrist