Bipolar Guidelines all in One

Psych Reads with Dr. Manish©

Dr.Manish Roshan
MD Psychiatry [AIIMS, New Delhi]
Organization Publication Date
Korean Medication Algorithm Project for Bipolar Disorder 2022 2022
(KMAP-BP 2022)

British Association for Psychopharmacology (BAP) 2016

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2018

2021 (Mixed)
2023 (Major Depressive Disorder
Update) (Cannabis use)

The International College of Neuropsychopharmacology Treatment Guideline for 2017

Bipolar disorder (CINP-BD-2017)

National Institute for Health and Clinical Excellence (NICE) 2014, 2018

Royal Australian and New Zealand College of psychiatrists clinical practice guidelines 2020
for mood disorders (RANZCP)

World Federation of Societies of Biological Psychiatry (WFSBP) 2009 (Acute Mania, Rapid Cycling)
2010 (Acute Depression)
2012 (Maintainance)
2018 (Mixed)
 Bipolar Disorder Treatment Guidelines - Acute Mania

Guidelines First Line Next-Step Intervention Later Intervention

KMAP-BP - 2022 Non-psychotic: Non-psychotic: Non-psychotic:

● Aripiprazole [ARP] ● Adding or replacing Mood Stabilizers or ● Two Mood Stabilizers + Atypical
● Lithium [Li] Atypical Antipsychotics Antipsychotics
● Olanzapine [OLZ] ● Mood Stabilizers + Atypical Antipsychotics ● Mood Stabilizers + Two Atypical
● Quetiapine [QTP] ● Two Mood Stabilizers Antipsychotics
● Valproate ● Two Mood Stabilizers + Two Atypical
Antipsychotics
Mood Stabilizers + Atypical Antipsychotics ● Clozapine
(ARP/OLZ/QTP/RIS) ● mECT

Psychotic: Psychotic: Psychotic:

● Aripiprazole [ARP] ● Adding or replacing Mood Stabilizers or ● Mood Stabilizers + Two Atypical
● Olanzapine [OLZ] Atypical Antipsychotics Antipsychotics
● Quetiapine [QTP] ● Mood Stabilizers + Atypical Antipsychotics ● Two Mood Stabilizers + Two Atypical
● Risperidone [RIS] ● Two Atypical Antipsychotics Antipsychotics
● Two Mood Stabilizers + Atypical ● Clozapine
Antipsychotics ● mECT
Mood Stabilizers + Atypical Antipsychotics
(OLZ/QTP/ARP/RIS)

Hypomania: Hypomania: Hypomania:

● Aripiprazole ● Adding or replacing Mood Stabilizers or ● Two Mood Stabilizers
● Lithium Atypical Antipsychotics (OLZ, RIS) ● Two Mood Stabilizers + Atypical
● Quetiapine ● Mood Stabilizers + Atypical Antipsychotics Antipsychotics
● Valproate ● Mood Stabilizers + Two Atypical
Antipsychotics
Mood Stabilizers + Atypical Antipsychotics ● Two Atypical Antipsychotics
(ARP/QTP) ● Typical Antipsychotics
BAP - 2016 Without AntiManic agent: Without AntiManic agent : Clozapine
● Alternative Anti Manic (Aripiprazole, other
Haloperidol, Olanzapine, Risperidone, antipsychotics, Carbamazapine, Lithium)
Quetiapine, Valproate

With Anti Manic: With AntiManic agent :

● Mood Stabilizers + Atypical Antipsychotics
● Optimization of anti manic agent
● Add Haloperidol, Olanzapine,
Risperidone, Quetiapine, another
Mood Stabilizer

CANMAT - 2018 Aripiprazole, Cariprazine, Risperidone, ● Olanzapine ● Carbamazepine

Paliperidone, Asenapine, Quetiapine, ● Carbamazepine ● Haloperidol + Lithium (or Valproate)
Valproate, Lithium ● Olanzapine + Lithium (or Valproate) ● Tamoxifen + Lithium (or Valproate)
----------------------------------------------------------- ● Lithium+Valproate ● Lithium(or Valproate)
Combination with Mood Stabilizers: ● Ziprasidone ● Clonazepam
Aripiprazole, Risperidone, Asenapine, and ● Haloperidol ● Clozapine
Quetiapine ● mECT ● rTMS
● mECT

CINP-BD - 2017 ● Aripiprazole ● Olanzapine ● mECT

● Cariprazine ● Lithium ● Oxcarbazepine
● Risperidone ● Carbamazepine
● Paliperidone ● Lithium (or Valproate) +
● Asenapine [ARP/HAL/OLZ/QTP/RIS]
● Quetiapine ● Lithium + Allopurinol
● Valproate ● Valproate + Typical Antipsychotics
● Valproate + Celecoxib
● Mood Stabilizers + Medroxyprogesterone

NICE - 2014 Without Anti-Manic agent: Alternative antipsychotics or adding Lithium or mECT
● Haloperidol Valproate
● Olanzapine
 ● Risperidone
● Quetiapine
With Anti-Manic agent:
● Optimization of anti manic agent
● Add
- Haloperidol
- Olanzapine
- Risperidone
- Quetiapine

RANZCP - 2020 Aripiprazole, Cariprazine, Risperidone, ● Carbamazepine mECT

Asenapine, Quetiapine, Valproate, Lithium ● Olanzapine
● Ziprasidone
Mood Stabilizers + Atypical Antipsychotics ● Haloperidol

WFSBP - 2009 Valproate, Aripiprazole, Ziprasidone, Optimize dosage Add-on with first-line agent
Risperidone Switch to another first-line agent; in severe Combination of two first-line choices
mania, consider combination

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 Bipolar Disorder Treatment Guidelines - Maintenance

Guidelines First Line Next-Step Intervention Later Intervention

KMAP-BP - Preventing mania: Preventing mania: Preventing mania:

2022 ● Mood Stabilizers ● Mood Stabilizers + Lamotrigine ● Mood Stabilizers + Atypical
● Mood Stabilizers + Atypical ● Two Mood Stabilizers Antipsychotics + Antidepressants
Antipsychotics (AAP) ● Mood Stabilizers + Atypical ● Atypical Antipsychotics +
● Aripiprazole Antipsychotics Antidepressants
● Quetiapine ● Antipsychotics + Lamotrigine ● Mood Stabilizers + Antidepressants
● Olanzapine ● Lamotrigine ● Antipsychotics + Lamotrigine
● Lamotrigine

Preventing depression: Preventing depression: Preventing depression:

● Mood Stabilizers + (AAP or LTG) ● Mood Stabilizers + Atypical ● Mood Stabilizers + Atypical
● Lamotrigine Antipsychotics + Lamotrigine Antipsychotics + Antidepressants
● Atypical Antipsychotics (Combination af three) ● Atypical Antipsychotics +
● Mood Stabilizers Antidepressants
● Atypical Antipsychotics + Lamotrigine ● Mood Stabilizers + Antidepressants
● Two Mood Stabilizers

BAP - 2016 Lithium If mania predominates: ● Combination therapy

● Valproate ● Antidepressants
● Olanzapine ● Clozapine
● Quetiapine ● Maintenance ECT
● Risperidone LAI
● Carbamazepine
● Oxcarbazepine

If depression predominates:
● Lamotrigine
● Quetiapine
CANMAT - 2018 ● Lithium ● Olanzapine ● Aripiprazole + Lamotrigine
● Quetiapine ● Risperidone LAI ● Olanzapine-Fluoxetine Combination
● Valproate ● Risperidone LAI (adj) ● Clozapine (adj)
● Lamotrigine ● Carbamazepine (CBZ) ● Gabapentine (adj)
● Asenapine ● Paliperidone
● Quetiapine + Li (or Val) ● Lurasidone + Li (or Val)
● Aripiprazole + Li (or Val) ● Ziprasidone+ Li (or Val)
● Aripiprazole
● Aripiprazole OM (Once Monthly)

CINP-BD - 2017 ● Lithium Add either of the following: Add either of the following:
● Quetiapine ● Fluoxetine or Lithium ● Risperidone LAI
● Olanzapine ● Li + CBZ ● Carbamazepine
● Paliperidone ● Quetiapine + Li (or Val) ● Lamotrigine
● Aripiprazole ● Mood Stabilizers + Olanzapine (or ● N-acetylcysteine
● Risperidone LAI Aripiprazole)
● Risperidone

NICE - 2014 Lithium ● Valproate Not mentioned

● Olanzapine
● Quetiapine

RANZCP - 2020 Preventing mania: Preventing mania: Olanzapine-Fluoxetine Combination

● Aripiprazole ● Paliperidone
● Lithium ● Risperidone
● Valproate ● Olanzapine
● Quetiapine ● Carbamazepine
● Asenapine ● Two Mood stabilizers
● Li + QTP ● Mood Stabilizers + Olanzapine (or
● Val + QTP Risperidone or Ziprasidone)
● Li + ARP

Preventing depression: Preventing depression:

● Lamotrigine ● Two Mood stabilizers
 ● Lithium, ● Mood Stabilizer + Olanzapine
● Valproate ● Mood Stabilizer + LTG
● Quetiapine ● LTG + Aripiprazole (or Olanzapine or
● Asenapine Quetiapine or Fluoxetine or
● Lithium + Quetiapine Lurasidone)
● Valproate + Quetiapine
● Lithium + Aripiprazole

WFSBP - 2012 ● Aripiprazole (mania and any ● Olanzapine (mania and any episode) ● Paliperidone (mania and any episode)
episode) ● Risperidone (mania and any episode) ● Antidepressant (Depression)
● Lamotrigine (Depression and any ● Valproate (Depression)
episode) ● Adjunctive Ziprasidone (mania and any
● Lithium (Any episode) episode)
● Quetiapine (Any episode)

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Bipolar Disorder Treatment Guidelines - Mixed

 Guidelines First Line Next-Step Intervention Later Intervention

KMAP-BP - Mixed mania: Mixed mania: Mixed mania

2022 ● Mood Stabilizers + Atypical ● Two Mood Stabilizers ● adding Antidepressants
Antipsychotics ● Lamotrigine + Atypical Antipsychotics
● Lithium ● Lamotrigine + Mood Stabilizers
● Quetiapine ● Lamotrigine
● Valproate ● Typical Antipsychotics
● Aripiprazole ● Carbamazepine
● Olanzapine ● Ziprasidone
● Risperidone
● Two Mood Stabilizers + Atypical
Antipsychotics
● Mood Stabilizers + Two Atypical
Antipsychotics
● Two Mood Stabilizers + Two Atypical
Antipsychotics
● Two Atypical Antipsychotics
● Lamotrigine + Atypical Antipsychotics
+ Mood Stabilizers

Mixed depression: Mixed depression: Mixed depression

● Mood Stabilizers + Atypical ● Two Mood Stabilizers + Atypical ● Switching Antidepressants
Antipsychotics Antipsychotics
● Lamotrigine + Atypical Antipsychotics ● Mood Stabilizers + Two Atypical
● Lamotrigine + Mood Stabilizers Antipsychotics
● Lamotrigine ● Two Mood Stabilizers + Two Atypical
● Lithium Antipsychotics
● Quetiapine ● Two Atypical Antipsychotics
● Valproate ● Lamotrigine + Atypical Antipsychotics
● Aripiprazole + Mood Stabilizers
● Olanzapine ● Mood stabilizers + Antidepressants
 ● Atypical Antpsychotics +
Antidepressants
● Typical Antipsychotics

Mixed bipolar: Mixed bipolar: Mixed bipolar

● Mood Stabilizers + Atypical ● Two Mood Stabilizers ● Atypical Antipsychotics +
Antipsychotics ● Lamotrigine + Atypical Antipsychotics Antidepressants
● Lithium ● Lamotrigine + Mood Stabilizers ● Mood Stabilizers + Antidepressants
● Quetiapine ● Lamotrigine
● Valproate ● Typical Antipsychotics
● Aripiprazole
● Olanzapine
● Lamotrigine

BAP - 2016 Same as for Mania Same as for Mania Same as for Mania

CANMAT - 2021 Mixed mania: Mixed mania: Mixed mania:

● None determined ● Asenapine ● Olanzapine
● Aripiprazole ● Carbamazepine
● Cariprazine ● Olanzapine + Mood stabilizers
Valproate ● Ziprasidone
● Quetiapine
● mECT

Mixed depression: Mixed depression: Mixed depression:

● None determined ● Cariprazine ● Olanzapine
● Lurasidone ● Carbamazepine
● Olanzapine + Mood stabilizers
● Olanzapine-Fluoxetine Combination
● Ziprasidone
● Quetiapine
● mECT
● Lamotrigine
 Mixed bipolar: Mixed bipolar: Mixed bipolar:
● Asenapine ● Valproate ● Ziprasidone
● Aripiprazole ● Olanzapine ● Cariprazine
● Carbamazepine ● Lithium + Valproate
● Olanzapine + Mood stabilizers ● Valproate + Carbamazepine
● mECT

CINP-BD - 2017 ● Olanzapine + Li (or Val) ● Carbamazepine ● Olanzapine-Fluoxetine Combination

● Aripiprazole ● Ziprasidone
● Olanzapine ● Valproate

NICE - 2014 Same as for Mania Same as for Mania Same as for Mania

RANZCP - 2020 ● Lithium Mixed mania: Adding on either Mixed mania:

● Valproate ● Asenapine ● Olanzapine + Mood stabilizers
● Quetiapine ● Aripiprazole
Mixed depression:
Mixed depression: Adding on ● Olanzapine-Fluoxetine Combination
● Lurasidone ● Olanzapine

Mixed bipolar: Mixed bipolar:

● Ziprasidone ● Carbamazepine
● Cariprazine

WFSBP - 2018 Mixed mania: Mixed mania: Mixed mania:

● Olanzapine + Valproate ● Aripiprazole ● Olanzapine
● Olanzapine ● Paliperidone ● Asenapine
● Quetiapine + Mood Stabilizers ● Carbamazepine + Lithium
● Carbamazepine
Mixed depression: ● Clozapine
● Ziprasidone ● Risperidone
● Cariprazine
● Ziprasidone
● Typical Antipsychotics
 ● Valproate
● mECT

Mixed depression:
● Olanzapine
● Carbamazepine
● Lurasidone
● mECT

---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Bipolar Disorder Treatment Guidelines - Rapid Cycling

 Guidelines First Line Next-Step Intervention Later Intervention

KMAP-BP - Currently manic: Currently manic: Currently manic:

2022 ● Mood stabilizers + Atypical ● Two Mood Stabilizers ● Mood Stabilizers + Antidepressants
Antpsychotics ● Lamotrigine + Atypical
● Lithium Antipsychotics
● Quetiapine ● Lamotrigine + Mood Stabilizers
● Valproate ● Mood Stabilizers + Typical
● Aripiprazole Antipsychotics
● Olanzapine ● Carbamazepine
● Risperidone ● mECT
● Lamotrigine
Currently depressed: Currently depressed:
Currently depressed: ● Two Mood Stabilizers ● Antidepressants
● Mood stabilizers + Atypical ● Mood Stabilizers + Atypical
Antpsychotics Antipsychotics + Antidepressants
● Lithium ● Atypical Antipsychotics +
● Quetiapine Antidepressants
● Valproate ● Mood Stabilizers + Antidepressants
● Aripiprazole ● Lamotrigine
● Olanzapine ● Mood Stabilizers + Typical
● Atypical Antipsychotics + Lamotrigine Antipsychotics
● Mood Stabilizers + Lamotrigine ● mECT

CINP-BD - 2017 ● Valproate ● Lithium ● Mood Disorders + Quetiapine (or

● Quetiapine ● Olanzapine Risperidone)
● Aripiprazole

NICE - 2014 Same as with other types of bipolar disorder

BAP - 2016 No Recommendation

CANMAT - 2018 No Recommendation

 RANZCP - 2020 No Recommendation

WFSBP - 2009 Not mentioned

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 Bipolar Disorder Treatment Guidelines - Bipolar Depression

Guidelines First Line Next-Step Intervention Later Intervention

KMAP-BP - Mild to Moderate: Mild to Moderate: ● Add or change to Clozapine

2022 ● Lithium ● Add Buspirone or stimulant or thyroid
● Lamotrigine ● Adding or change Mood Stabilizers or hormone
● Quetiapine (QTP) Atypical Antipsychotics or Lamotrigine ● mECT
● Valproate ● Mood Stabilizers + LTG ● rTMS
● Aripiprazole (ARP) ● Two Atypical Antipsychotics
● Olanzapine (OLZ)
● Mood Stabilizers + Atypical
Antipsychotics (ARP/QTP/OLZ)
● Lamotrigine + Atypical Antipsychotic
(ARP/QTP/OLZ)

Non-Psychotic Severe: Non-Psychotic Severe:

● Mood Stabilizers + Atypical
Antipsychotics (ARP/QTP/OLZ) ● Change Mood stabilizers or Atypical
● LTG + Atypical Antipsychotics Antipsychotics
(ARP/QTP/OLZ) ● Mood Stabilizers + Atypical
● Mood Stabilizers + LTG Antipsychotics + Lamotrigine
● LTG + Atypical Antipsychotics
● Two Mood Stabilizers + Atypical
Antipsychotics
● Mood Stabilizers + Two Atypical
Antipsychotics
● Lamotrigine + Two Atypical
Antipsychotics
● Mood stabilizers + Antidepressants
● Atypical Antipsychotics +
Antidepressants
 Psychotic: Psychotic:
● Mood Stabilizers + Atypical
Antipsychotics ● Mood Stabilizers or Atypical
(ARP/QTP/OLZ/Risperidone) Antipsychotics
● LTG + Atypical Antipsychotics ● Mood Stabilizers + LTG
● Mood Stabilizers + Atypical
Antipsychotics + Lamotrigine
● LTG + Atypical Antipsychotics
● Two Mood Stabilizers + Atypical
Antipsychotics
● Mood Stabilizers + Two Atypical
Antipsychotics
● Lamotrigine + Two Atypical
Antipsychotics
● Mood stabilizers + Antidepressants
● Atypical Antipsychotics +
Antidepressants

BAP - 2016 Without Antimanic agents: Anti depressant Combination

● Lamotrigine mECT
● Quetiapine (QTP)
● Lurasidone
● Olanzapine (OLZ)
● Lamotrigine combination

With Antimanic optimization:

● Lamotrigine
● Quetiapine (QTP)
● Lurasidone
● Olanzapine (OLZ)
● Consider mECT in severe depression

CANMAT - 2018 ● Quetiapine (QTP) ● Valproate ● Carbamazepine

● Lurasidone + Lithium (or Valpraote) ● SSRI/Bupropion (adj)
 ● Lamotrigine ● mECT Adjunctive:
● Lamotrigine (adj) ● Cariprazine ● Olanzapine
● Olanzapine-Fluoxetine ● SNRI/MAOi
Combination ● Modafinil
● Eicosapentanoic Acid
● rTMS
● Ketamine
● Light Therapy/Sleep deprivation
● Levothyroxine
● N-Acetylcystine
● Pramipexole
● Aripiprazole
● Armodafinil
● Asenapine

CINP-BD - 2017 ● Quetiapine ● Valproate ● Aripiprazole

● Lurasidone ● Lithium ● Imipramine
● Olanzapine-Fluoxetine ● Mood Stabilizers + (or Modafinil or ● Phenezine
Combination Pramipexole) ● Lithium + Oxcarbazapine (or
● Lithium + Pioglitazone L-Sulpiride)
● Add Escitalopram or Fluoxetine

NICE - 2014 Without Antimanic agents: Adding Lamotrigine

● Lamotrigine
● Quetiapine (QTP)
● Olanzapine (OLZ)
● Olanzapine-Fluoxetine Combination

With Antimanic optimization:

● Lamotrigine
● Quetiapine (QTP)
● Lurasidone
● Olanzapine (OLZ)
● Consider mECT in severe depression
RANZCP - 2020 ● Lithium ● Two Mood Stabilizers ● Carbamazepine
● Quetiapine ● Mood Stabilizers + Atypical ● Olanzapine
● Valproate Antipsychotics ● Asenapine (adj)
● Lamotrigine ● Mood Stabilizers + ● Armodafinil (adj)
● Lurasidone ● Two Mood Stabilizers + Two Atypical ● Levothyroxine (adj)
● Cariprazine Antipsychotics
● Mood stabilizers + Antidepressants
● Mood stabilizers + Two
Antidepressants
● Atypical Antpsychotics +
Antidepressants
● mECT

WFSBP - 2010 ● Lithium ● Optimization of first line treatment

● Quetiapine ● Quetiapine
● Valproate ● Add on
● Olanzapine 1. Carbamazepine
● Olanzapine-Fluoxetine Combination 2. Lithium
● Lamotrigine + Lithium 3. Modafinil +
● Lamotrigine Li/Val/Antidepressants
4. mECT
 Recommendations on Cannabis use in Bipolar Disorder and Major Depressive Disorder

Recommendations

CANMET- 2023 Findings:

● Daily tobacco use was significantly more prevalent in individuals with BD who used cannabis in the past 6 months compared to
those who did not.
● In Bipolar Disorder, Cannabis Use Disorder (CUD) was associated with a fourfold risk of nicotine dependence
● Alcohol use was more common in individuals with BD who use cannabis compared to those who do not.
● CUD in BD was correlated with a higher risk of alcohol misuse.
● Cannabis use (CU) increases the first episode of BD.
● BD onset is earlier in cannabis users by up to 9 years.
● Higher cannabis use correlates with earlier BD onset.
● Cannabis Use Disorder (CUD) also correlates with earlier BD onset.
● BD with CU is associated with more frequent rapid cycling.
● History of Long Term-Cannabis Use and CUD is linked to earlier hospitalizations.
● BD with current CU is associated with an increased recurrence rate.
● Recurrence levels in individuals with BD who cease CU are comparable to those who never used cannabis.
● The data indicate that cannabis use is associated with worsened course and functioning of bipolar disorder and major depressive
disorder

Recommendations:
● Inconsistency in cannabis effects in MDD contributes to a qualified recommendation against its use in this disorder.
● Clinicians should inquire about cannabis use to understand potential associations between alterations and clinical
symptomatology.
● Three dimensions of cannabis use should be explored: course of use, content, and context of use.
● Cannabis use during pregnancy is an emerging phenomenon associated with MDD.
● Psychosocial interventions, particularly motivational enhancement therapy and CBT, have been associated with a reduction in
cannabis use.

There was no recommendation from any other organization.

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