Re:The role of dopamine transporter single photon emission CT (DaT-SPECT) in the diagnosis of drug-induced Parkinsonism.

Igor Grachev, ,

Other Contributors:

September 19, 2013

We thank Dr McKinley for his correspondence on our paper entitled "Clinical utility of dopamine transporter single photon emission computed tomography (DaTspect) with [123I] ioflupane in diagnosis of parkinsonian syndromes".

Although suspected drug-induced parkinsonism (DIP) was not a direct focus of our review, we included DIP cases and discussed them as being either suspected/uncertain parkinsonian syndromes (PS) or as subjects with scans without dopaminergic deficit (SWEDD).

A direct discussion on DIP was not included as DaTscan is not approved for the differential diagnosis between DIP and idiopathic Parkinson's disease (IPD), and additional registration studies and regulatory efforts would be needed to confirm such utility and update the product label. We are aware that many clinicians already utilise DaTscan in an off licensed indication for this clinical question.

DIP is a heterogeneous disorder due to a variety of drug classes (discussed in 1). Most have clear post-synaptic dopaminergic receptor blockade (tardive parkinsonism), but there are other cases where dopaminegic blockers have exacerbated/unmasked prodromal pre-synaptic PD and lastly cases where a combination of pre- and post-synaptic dopaminergic effects are speculated (2, 3).

DaTscan would not be able to differentiate these latter two diagnoses with both showing an abnormal scan. Similarly, a normal DaTscan does not confirm tardive parkinisonism in this clinical context as normal DaTscan is seen in other types of parkinsonism (e.g., psychogenic, vascular, dopa- responsive dystonia etc.) This heterogeneity is reflected in DaTscan studies showing a mixture of normal and abnormal scans (from <10% to >50%) in the DIP population (2, 4).

In addition, studies demonstrated lower striatal dopamine transporter binding in neuroleptic-naive schizophrenic patients that were not related to anti-psychotic treatment suggesting a dopamine transporter deficit as a potential illness trait (3), and/or implying existence of pro-Parkinsonian risk factors independent of drugs in patients with schizophrenia.

Future research utilizing prospective and controlled study designs are warranted to clarify the underpinning mechanisms of developing DIP, and the direct mode of developing of parkinsonism in patients receiving calcium channel blockers, first generation anti-histamine drugs, valproate, lithium and other dopaminegic blockers.

References

1. Bondon-Guitton E, Perez-Lloret S, Bagheri H, Brefel C, Rascol O, Montastruc JL. Drug-induced parkinsonism: a review of 17 years' experience in a regional pharmacovigilance center in France. Mov Disord. 2011 Oct;26(12):2226-31. 2. Tinazzi M, Cipriani A, Matinella A, Cannas A, Solla P, Nicoletti A, Zappia M, Morgante L, Morgante F, Pacchetti C, Sciarretta M, Dallocchio C, Rossi S, Malentacchi M, Ceravolo R, Frosini D, Sestini S, Bovi T, Barbui C. [???I]FP CIT single photon emission computed tomography findings in drug-induced Parkinsonism. Schizophr Res. 2012 Aug;139(1-3):40-5. 3. Mateos JJ, Lome?a F, Parellada E, Mireia F, Fernandez-Egea E, Pavia J, Prats A, Pons F, Bernardo M. Lower striatal dopamine transporter binding in neuroleptic-na?ve schizophrenic patients is not related to antipsychotic treatment but it suggests an illness trait. Psychopharmacology (Berl). 2007 Apr;191(3):805-11. 4. Diaz-Corrales FJ, Sanz-Viedma S, Garcia-Solis D, Escobar-Delgado T, Mir P. Clinical features and 123I-FP-CIT SPECT imaging in drug-induced parkinsonism and Parkinson's disease. Eur J Nucl Med Mol Imaging. 2010 Mar;37(3):556-64.

Conflict of Interest:

NB: Since 2002, has received grants from GE Healthcare (2005), Parkinson's UK (2011, 2012), MRC (2011) and the Sarah Matheson Trust (2004); has received honoraria for lecture fees from GE Healthcare, UCB Pharma, Teva Lundbeck, GSK, Genus Pharma; has received honoraria for advisory boards for UCB, GSK, GE Healthcare. IDG is an employee of GE Healthcare. RAH has received honoraria or payments for consulting, advisory services, speaking services over the past 12 months as listed below: Abbott Laboratories, Allergan, Inc., AstraZeneca, Biotie Therapies Corporation, Ceregene, Chelsea Therapeutics, GE Healthcare, Impax Laboratories, Ipsen Biopharmaceuticals, Lundbeck, Med-IQ, Merck/MSD, Noven Pharmaceuticals, Straken Pharmaceuticals, Targacept, Teva Pharmaceuticals Industries, Teva Neuroscience, Upsher-Smith Laboratories, UCB, UCB Pharma SA, Xenoport, RAH's institution has received research support over the past 12 months as listed below: Abbot Laboratories, Addex Therapeutics, Allergan, AstraZeneca, Chelsea Therapeutics, GE Healthcare, Impax Laboratories, Ipsen Biopharmaceuticals, Merck/MSD, Merz, Michael J Fox Foundation for Parkinson's Research, Schering-Plough, Teva Neuroscience, UCB, Vita-Pharm. RAH has received royalties in the last 12 months: University of South Florida. In addition, RAH has consulted in litigation with lawyers representing various current and former manufacturers of welding consumables.

Conflict of Interest

None declared