Transcript Drugs → brain structures AP MST Bipolar disorder NICE Diagnosis

Drugs → brain structures
AP
MST
Bipolar disorder
NICE
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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
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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)
NICE
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Before a rapid cycling BD is diagnosed
consider:
Erratic compliance
hypothyroidism, AD, suboptimal medication
regimes
Lithium withdrawal
NICE
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Consider a diagnosis of BD before Axis II if
there are mood swings
During treatment consider compliance before
considering a personality disorder
NICE
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Treatment (1/3)
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Inform the patient
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Contraception and risk of pregnancy
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See patients once / (1|2) week (for 3 months)
NICE
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Treatment (2/3)
Acute mania (and mixed→ AP, valproate,
lithium, BDZ
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AP (olanz, risp, quet)→ severe manic symptoms |
marked behavioral disturbances
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Valproate or lithium → previous response, good
compliance, augmentation of AP
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Lithium → not severe symptoms
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NOT RECOMMENDED: CBZ, Gabapent, Lamo
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Treatment (3/3)
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Acute depression
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Add AP (quetiapine) to AD (SSRI better than TCI)
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No AD → rapid-cycling, recent hypomanic, recent
functional impairing and rapid mood fluctuations
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Stop AD → after 8 weeks of symptoms relief
(parox, venlafax → higher risk of discontinuation
syndrome)
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Avoid → Lamo a single treatment for BDI
Mania, which treatment ?
3 weeks
Mania, which treatment ?
Mania, which treatment ?
Change in mania rating scores
Mania, which treatment ?
Risk difference for treatment responders
Mania, which treatment ?
Risk difference for drop outs
Conclusion 1
Use second generation AP (risp, olanz, quet) for
the treatment of acute mania (3 weeks)
Mood stabilizers are second choice
Acute depression, which treatment ?
Acute depression, which treatment ?
Acute depression, which treatment ?
Symptom
remission
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
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
Maintenance → lithium
Lithium 41% vs
61% placebo
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
neuroimaging
lithium
neuroimaging
1.9 years base-1st fu
4 years base-2nd fu
Valproate and AP
Overall, no significant brain volume modification
in bipolar patients taking valproate or AP
Valproate
ant
AP mechanism
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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
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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
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
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
imaging
Conclusion 5
Lymbic structures and the PFC are key relay
points for the efficacy of pharmacological
treatments in BP
Schizophrenia
skz
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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
skz
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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
skz
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Which drug ?
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
imaging
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
II AP → ↑ glutamatergic turnover and inhibit
NMDA receptors
17 (8m/9f) acute psychotic recurrentepisode (chronic) patients treated with
haloperidol or risperidone
30 medication-naive first-episode patients and 36 matched
healthy controls participated
Atypical antipsychotic treatment
Effect of practice
on brain
activation in the
left dorsolateral
prefrontal cortex
(DLPFC)
8 skz and 8 controls
Treated with risperidone for 6 weeks
Conclusion 7
II AP increase the DLPC activity
This event correlates with outcome
Variations in the NAc may be involved during
withdrawal