Psychiatrische bijwerkingen van somatische medicatie
Rob Heerdink
Dr Rob Heerdink Pharmacoepidemiology & Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences Universiteit Utrecht The Netherlands
www.uu.nl/science/pharmacoepidemiology
Dr Rob Heerdink Pharmacoepidemiology & Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences Universiteit Utrecht The Netherlands
www.uu.nl/science/pharmacoepidemiology
Psychiatrische bijwerkingen van somatische medicatie “Neuropsychiatrisch” DSM-5 Hoofdpijn? Misselijkheid? Slaapproblemen? Libido?
Psychiatrische bijwerkingen van somatische medicatie Depressieve klachten Psychotische klachten Slaapproblemen Gedragswijzigingen
Psychiatrische bijwerkingen van somatische medicatie
Pharmacopsychiatry 2013
3.0*
3.0*
3.0*
3.0*
3.0*
3.0
3.0
3.0*
3.0
3.0
Mediaan aantal medicaties gebruikt voor somatische aandoeningen per patiënt.
Figuur 1: Proportie van patiënten die 1, 2 en ≥3 medicaties gebruikten voor somatische aandoeningen op elk prevalentiepunt. Mediaan: 3.
Any somatic medication (%) Acid & bowel related medications (%) Laxatives (%)
Anti‐diabetics (%)
Cardiovascular medications (%) Lipid lowering medications (%) Asthma and COPD medications (%)
Analgesics and antirheumatics (%)
Vitamins (%)
OVERALL 886 76.9 25.6 23.3 11.1 22.2 11.1 12.9 3.4 5.6 3.0 34.0 11.3 21 24.2
Vrouwen 397 76.8 29.7 30.2 10.8 24.9 10.1 13.9 4.8 10.1 2.3 39.5 10.8 20.7 21.2
Mannen 489 76.9 22.3 17.6 11.2 20.1 11.9 12.1 2.2 2.0 3.7 29.4 11.7 21.3 26.6
Anti‐cholinergic medications (%)
Dermatologicals (%)
Systemic antifungals and antibiotics (%)
Thyroid medications (%)
Antihistamines (%)
Total patients (N)
Prevalentie
Bloed-hersen-barrière
Bloed-hersen-barrière
Bloed-hersen-barrière
Bloed-hersen-barrière
Bloed-hersen-barrière • • • • •
Meninigitis Multiple sclerose Epilepsie Alzheimer HIV
Antidepressants
Pharmaceutical regulation has been always driven by crises, e.g. Thalidomide (Softenon, 1961) Mibefradil (Posicor, 1998) Rofecoxib (Vioxx, 2004) Heparin (several products, 2008) Rosiglitazon (Avandia, 2010)
22-5-2015
Leufkens 2015 17
The best moment to bring a product to the clinic?
Eichler HG, Pignatti F, Flamion B, Leufkens H, Breckenridge A. Balancing early market access to new drugs with the need for benefit-risk data. Nat Drug Discov 2008; 7: 818-26.
22-5-2015
Leufkens 2015 18
Lareb signalen 1998 -2015 drug
outcome
mechanism
dextromethorphan
Neuropsychiatric symptoms
passes BBB
ACE-inhibitors
hallucinations
Enzyme red->opioid+?
ACE-inhibitors
nightmares
?
Losartan
Sleep/depressed/hallucina tions/nightmares
?
AII-antagonists
Nightmares
?
Bisphosphonates
depression
?
Gabapentin
Sexual disorders
GABA+
Goserelin
Depression/lability/psycho sis
Testosteron inhibition
Statins
Nightmares
Tryptophan+ -> dopamine+?
Lamotrigine
Nightmares
REM-sleep disturbance?
Montelukast
Depressive symptoms
?
Tamsulosin
Depressive reactions
?
Phase I to III research not very informative on safety Very few RCTs primarily aimed at side effects Pre-registration period (phase I to III studies) • Only frequent side effects known (small RCTs) • Often not measured (not expected, no suspicion) • Follow-up period often too short • Other restrictions to trials
The likelihood of observing an adverse drug reaction employing numbers usually studied in premarketing trials (n=2,000) Threshold for ADR
Probabilit y
1/500 (Lymphoma From Azathioprine)
0.98
1/1,000 (Eye damage from practolol)
0.86
1/10,000 (Anaphylaxis from penicillin)
0.18
1/50,000 (Aplastic anemia from chloramphenicol)
0.04
Lembit Rägo, WHO Upsala
Casus Tamiflu
Casus Tamiflu
Casus Tamiflu
Casus Propanolol
- Serotonerg - Lipofiel >25 studies Conclusies????
Psyfar december 2012
Casus anticholinergica Centrale anticholinerge symptomen: cognitie-, verwardheid, geheugenproblemen, agressie, delier Anticholinerge schalen: >10 Verband met delier: lastig Verband met agressie:
The association between the anticholinergic load and aggressive behavior in nursing home patients with dementia: a nested case control study. J. Los, A Egberts, E.R. Heerdink. Under review
Totale populatie Hoge anticholinerge load -> geen significant effect Populatie met pijnklachten Hoge anticholinerge load -> verhoogd risico op agressie
Determinant
Uitkomst
Hoge exposure
Slecht gedefinieerd
Polyfarmacie
Slecht gemeten
Kwetsbare patiënten
Mechanisme onbekend
RCTs weinig informatief
RCTs weinig informatief
evidence based medicine
medicine based evidence pharmacoepidemiology
Registration of a drug is only the beginning of safety research
email:
[email protected] twitter: @robheerdink www.slideshare.net/robheerdink
