1. Drugs → brain structures AP MST

2. Bipolar disorder

3. NICE Diagnosis Full history of the patient (family, any episode, symptoms between the episodes) Symptoms profile, triggers to previous episodes, social and personal functioning, comorbidities, physical health, current psychosocial stressors Interview a family member

4. NICE BE CAREFUL If (Psychotic symptoms, ↑ suicidal ideation, ↑ drug misuse) → late BD and not SKZ (minorities) If alcohol | drug → wait 7 days before diagnosis Late onset (>40yrs) → hypothyroidism, stroke, neurological disorders (dementia)

5. NICE Before a rapid cycling BD is diagnosed consider: Erratic compliance hypothyroidism, AD, suboptimal medication regimes Lithium withdrawal

6. NICE Consider a diagnosis of BD before Axis II if there are mood swings During treatment consider compliance before considering a personality disorder

7. NICE Treatment (1/3) Inform the patient Contraception and risk of pregnancy See patients once / (1|2) week (for 3 months)

8. NICE Treatment (2/3) Acute mania (and mixed→ AP, valproate, lithium, BDZ  AP (olanz, risp, quet)→ severe manic symptoms | marked behavioral disturbances  Valproate or lithium → previous response, good compliance, augmentation of AP  Lithium → not severe symptoms  NOT RECOMMENDED: CBZ, Gabapent, Lamo

9. NICE Treatment (3/3) Acute depression  Add AP (quetiapine) to AD (SSRI better than TCI)  No AD → rapid-cycling, recent hypomanic, recent functional impairing and rapid mood fluctuations  Stop AD → after 8 weeks of symptoms relief (parox, venlafax → higher risk of discontinuation syndrome)  Avoid → Lamo a single treatment for BDI

10. Mania, which treatment ? 3 weeks

11. Mania, which treatment ?

12. Change in mania rating scores

13. Mania, which treatment ? Risk difference for treatment responders

14. Mania, which treatment ? Risk difference for drop outs

15. Conclusion 1 Use second generation AP (risp, olanz, quet) for the treatment of acute mania (3 weeks) Mood stabilizers are second choice

16. Acute depression, which treatment ?

19. Symptom remission

20. Conclusion 2 Use second generation AP (olanz, quet) for the treatment of acute depression during BD Mood stabilizers are less efficacious No strong evidence for using SSRI

21. Maintenance, which treatment ? the same regimen that successfully treated the acute bipolar mood episode attempt monotherapy. However, many bipolar patients require medication combinations First line: lithium, lamotrigine, risperidone (im) Second line: aripiprazole, valproate, quet, olanz Suicide risk → lithium

22. Maintenance → lithium

25. Lithium 41% vs 61% placebo

33. Conclusion 3 For maintenance use the same drug started during acute phase If not possible use lithium, risperidone im, lamotrigine, valp Start with monotherapy, but multitreatment is more effective

34. neuroimaging

35. lithium

38. neuroimaging

39. 1.9 years base-1st fu 4 years base-2nd fu

43. Valproate and AP Overall, no significant brain volume modification in bipolar patients taking valproate or AP

44. Valproate

46. ant

47. AP mechanism Serotonin-glutamate Type II metabotropic glutamate receptors (mGluRs) and serotonin 5-HT(2A) receptors have been reported to form heterodimers that modulate G-protein-mediated intracellular signaling differentially compared to mGluR2 and 5-HT(2A) homomers

48. Serotonin-Dopamine-Scaffolding The scaffolding protein PSD-95 is known to interact with N-methyl-D-aspartate (NMDA), D(2) and 5-HT(2) receptors, regulating their activation state

49. Homer1a, the inducible member of the Homer family of PSD proteins that is implicated in glutamatergic signal transduction, is induced in striatum by antipsychotics with high dopamine receptor affinity and in the cortex by antipsychotics with mixed serotonergic/dopaminergic profile

51. Conclusion 4 The molecular events that drive the efficacy of mood stabilizers are related to GSK-3, IPP and prosurvival genetic expression The dopaminergic-serotoninergic-glutamatergic balance is central to the activity of AP in the prefrontal cortex. Scaffolding proteins are thought to be relevant

52. imaging

61. Conclusion 5 Lymbic structures and the PFC are key relay points for the efficacy of pharmacological treatments in BP

62. Schizophrenia

63. skz Treatment First episode → oral AP, address to specialized unit, write a care plan in collaboration with the patient and send it to the GMP, include a crisis plan Provide information and discuss the benefits and disadvantages Chose the AP with the patient, taking into consideration extrapyramidal side effects and metabolic side effects Assess the cardiovascular risk (ECG)

64. skz Start with the lower dose of AP Justify and record reasons for dosages outside the range given by guidelines Monitor efficacy, side effects, adherence, physical health Record the rationale for continuing, changing or stopping medication and the effects of such changes Trials for one medication should last 4-6 weeks Do not “neuroleptisize” your patient Rapid tranquillization

65. skz Which drug ?

78. Conclusion 6 Second generation AP are more effective for the treatment of Skz Use Olanzapine and Risperidone when possible The side efffect profile must nevertheless guide the clinical choices

79. imaging

80. Conventional antipsychotic agents led to an increase of basal ganglia volume while ongoing multifocal gray matter loss Modern atypical agents rather tend to turn increased basal ganglia volume back to normal while increasing the volume of thalamus and of gray matter in different key regions

81. II AP → ↑ glutamatergic turnover and inhibit NMDA receptors

85. 17 (8m/9f) acute psychotic recurrent- episode (chronic) patients treated with haloperidol or risperidone

88. 30 medication-naive first-episode patients and 36 matched healthy controls participated Atypical antipsychotic treatment

91. Effect of practice on brain activation in the left dorsolateral prefrontal cortex (DLPFC)

98. 8 skz and 8 controls Treated with risperidone for 6 weeks

103. Conclusion 7 II AP increase the DLPC activity This event correlates with outcome Variations in the NAc may be involved during withdrawal