Schizophrenia and Driving

Schizophrenia

Schizophrenia is a serious brain disorder where people interpret reality abnormally. Often this illness manifests in some combination of hallucinations, delusions, and extremely disordered thinking and behaviour. (1)

Symptoms, Causes, Risk Factors, Complications, Tests and diagnosis, Prevention, Treatments and Drugs Used in Schizophrenia

The Mayo Clinic provides an excellent summary of the major symptoms, causes, risk factors, complications, tests and diagnosis, prevention ,treatments and current drugs used in the management of schizophrenia patients .(2-8)

Incidence of Schizophrenia

The world health organization estimates that there are more than 21 million people worldwide who suffer from schizophrenia. (9)

However John J McGrath reported that there was a very widespread range in the incidence of schizophrenia worldwide.

He suggested that based on conservative estimates, there was a 5 fold variation in the incidence of schizophrenia ranging from 7.7 to 43.0 per 100, 000. (10)

The illness occurred more frequently in men compared to women [ratio of males to females being 1.4 to 1]. (11, 12)

Interestingly, 2 reviews found that migrants also had a significantly 3 to 5 increased risk ratio of developing schizophrenia. (13, 14)

Early Findings of Driving Impairment Among Schizophrenics

In 1993, Wylie and colleagues compared 22 patients who received depot neuroleptics for chronic schizophrenia with 16 control subjects in their performance on simulated driving tests.

They observed that there was a significant decrement in driving performance in subjects treated with neuroleptics compared with the control group. (15)

However 6 years later, H J Grabe and colleagues compared 10 clozapine-treated patients with 18 who were taking the classical neuroleptics. (16)

They investigated psychomotor performance of schizophrenic inpatients measuring reaction time, vigilance, visual perception and stress tolerance and the data was collected by technical equipment (Act and React Testsystem).

The patients' driving ability turned out to be equally impaired in both treatment groups.

While 11% of the patients passed all tests without major impairment; 32% of the patients showed some impairments that required individual evaluation of their driving ability.

However, 57% were considered to be severely impaired and the driving of vehicles could not be recommended for those patients.

In 2002, Palmer and colleagues compared 83 middle-aged and elderly outpatients with schizophrenia (mean age 59 years) with 46 demographically equivalent normal comparison subjects. (17)

They also found that the schizophrenia patient group had consistently worse functional status than the control group.

Interestingly, they observed that the severity of negative symptoms (but not that of positive symptoms) was inversely correlated with functional status.

However the following year, S Kagerer and co-workers examined 49 participating patients that were examined at discharge following psychopathological stabilisation. (18)

Their study was designed to evaluate the effects of atypical neuroleptics in comparison with a conventional dopamine antagonist neuroleptic (haloperidol) on several dimensions of psychomotor performance (visual perception, attention, reaction time, and sensorimotor performance) considered to be of relevance in evaluating driving fitness.

Twenty subjects received haloperidol and 29 received an atypical neuroleptic.

The psychomotor performance was assessed by means of the ART 90, a computerized Act and React Test which is generally used in diagnosis of psychomotor performance.

The study results demonstrated a remarkably reduced psychomotor performance in the haloperidol-treated group of schizophrenic patients compared with patients treated with atypical neuroleptics.

Only 1 (5%) subject passed all subtests without major failures and could be regarded as competent to drive.

Among patients with atypical neuroleptics, 7 patients (24%) passed all test parameters without major failures.

In 2004, A Brunnauer and colleagues studied the effects of neuroleptic mono-therapy on psychomotor functions related to car driving skills in schizophrenic patients, (19)      

120 consecutively admitted schizophrenic inpatients were tested under steady state plasma level conditions before discharge to outpatient treatment.

Patients met the International Classification of Diseases, Tenth Revision criteria for schizophrenia.

The study followed a naturalistic non-randomized design.

Data were collected with the computerized Act & React Testsystem and were analysed according to medication, severity of illness, and age.

Only 32.5% of the schizophrenic inpatients passed the tests without major impairments.

Those patients that were treated with atypical neuroleptics or clozapine showed a better test performance on skills related to driving ability when compared with patients on typical neuroleptics.

Differences were most evident in measures of divided attention, stress tolerance, and attention.

In 2005, M Soyka and fellow investigators evaluated 40 participating patients that were examined at discharge following psychopathological stabilisation. (20)

Twenty subjects received haloperidol medication and 20 received the atypical neuroleptic risperidone.

A control group consisted of 19 healthy individuals.

The authors found a remarkably reduced psychomotor performance in both groups of schizophrenic patients compared to healthy controls.

Furthermore, only one (5%) subject passed all subtests without major failures and could be regarded as competent to drive.

 Among patients given risperidone, seven patients (35%) passed all test parameters without major failures.

Schizophrenia was also among the numerous conditions that S C Marshall found was associated with an increased crash risk in elderly drivers. (21)

Driving simulator performance and psychomotor functions of schizophrenic patients treated with antipsychotics.

More recently, Alexander Brunnauer and his co-investigators tested 80 patients before they were discharged to outpatient treatment.

They found that 25% of schizophrenic patients were considered as severely impaired with respect to driving skills. (22)

The authors collected data with the computerized Act & React Testsystem and the Wiener Testsystem measuring visual perception, reaction time, attention, vigilance and stress-tolerance.

 Patients undertook various driving simulations on a static driving simulator (FT-SR 200).

Differences between treatment groups were shown both for psychomotor measures and in driving simulator performance with a patients being treated with atypical antipsychotics performing better.

Inpatients were controlled for age, psychopathologic symptoms and extra-pyramidal signs

Differences in psychomotor measures were most pronounced in vigilance and concentration.

Furthermore in 2012, A Brunnauer and G Laux conducted a non-randomized clinical study with 30 schizophrenic in patients receiving sertindole (n=10), risperidone (n=10) or quetiapine (n=10). (23)

These patients were evaluated under steady-state plasma level conditions prior to discharge to outpatient treatment.

Data were collected with the computerized Act and React Testsystem (ART90) and the Wiener Determinationsger?t (WDG) measuring psychomotor skills relevant for fitness to drive.

There were 2 main findings of this study.

• Approximately 26% of schizophrenic patients, -following psychopathologic stabilization and prior discharge to outpatient treatment showed severe impairments with respect to driving skills.
• Statistically significant differences between atypical antipsychotics could not be demonstrated for the level of the global driving ability score nor on individual functional domains essential for fitness to drive.

However in an earlier study, B Gallhofer and colleagues contrasted the impact of sertindole and haloperidol on cognitive function in patients suffering from schizophrenia. (24)

They conducted a 12 week trial of 40 patients randomised to treatment, 34 (17 sertindole and 17 haloperidol) were included in the analysis set.

Cognitive sub-processes were investigated with the Reaction Time Decomposition (RTD) method and the Wisconsin Card Sorting Test (WCST), at Baseline and after 4 and 12 weeks of therapy.

Possessing a larger sample size for analysis, they were able to show that that after 12 weeks of treatment the sertindole (all-patients) group was faster in the simple reaction task (183 ms; p 0.01), the stimulus discrimination task (162 ms; p 0.01), and the choice reaction task (210 ms; p 0.01) than the haloperidol group.

More recently, L Lipskaya-Velikovsky and colleagues demonstrated that visual perception deficits in schizophrenia did not prevent clients from driving, and general cognitive status appeared to be a valid determinant for actual driving. (25)

They suggested usage of a general test of cognition such as Mini-Mental State Examination, or conjunction number of cognitive factors such as executive functions (e.g., Trail Making Test) and attention (e.g., Continuous Performance Test) in addition to spatial-visual ability tests (e.g., Rey-Osterrieth Complex Figure test) for considering driving status in schizophrenia.

Further data from G Laux and A Brunnauer concluded that around 17?% of remission bipolar patients must be regarded as unable to drive and 27?% of patients with schizophrenia on discharge from hospital.(26)

Criteria for Driving Ability in Psychosis

Acute psychotic illness rules out driving ability.

For patients with first onset disease this can usually be granted after 1 year of remission from symptoms but in cases of repeated exacerbation's longer intervals of 3-5 years are warranted. (27)

In the United Kingdom you have to tell the Drivers and Vehicle Licensing Agency (DVLA) if you have certain mental illnesses or take some medication. (28)

For long-lasting psychosis or schizophrenia you must:

• Have stayed well and stable for at least 3 months,
• Agreed to maintain your treatment regime,
• Not have any side effects from medication that impact you’re driving
• Have a report from your doctor that said you are well enough to drive

However if you do have ongoing symptoms, this does not prevent you from having a license.

Nevertheless to have a licence, your ongoing symptoms must be unlikely to cause problems:

• With your concentration,
• With your memory, or
• That would distract you while driving your vehicle

Is there any difference between driving skills in unmedicated first- and recurrent-episode schizophrenics?

FM Segmiller and co-workers examined driving skills according to regulations of the German guidelines for road and traffic safety in unmedicated schizophrenic inpatients. (29)

A total of 13 first-episode (FES) and 13 recurrent-episode (RES) schizophrenic inpatients were included in the analysis and compared with a group of 20 healthy controls (HC).

Their data was collected with the computerized Wiener Testsystem measuring visual perception, reactivity and stress tolerance, concentration and vigilance.

Analysis of data indicates that a great proportion (58 %) of schizophrenic patients were impaired in psychomotor functions related to driving skills.

FES and RES significantly differed with respect to driving ability with a greater proportion in the FES (38 %) showing severe impairments when compared with RES (25 %).

Differences with respect to healthy control performance were most pronounced in concentration and for the FES additionally in visual perception.

Analysis of their data indicates that a great proportion of schizophrenic patients are impaired in psychomotor functions related to driving skills that cannot be attributed to adverse side effects of psycho-pharmacological treatment.

Furthermore the authors could not confirm a chronical decline of psychomotor functions related to driving skills at least in the early course of schizophrenic illness.

High Incidence of Motor Vehicle Accidents in Schizophrenic and Schizoaffective Disorder Patients

A Leroy and M Morse had found that The Odds Ratio (OR) for motor vehicle crashes associated with the use of atypical antipsychotics was significant at 2.20 [ P  .01] (30)

This was further explored by T Steinert and colleagues who examined the patterns of individual mobility in a representative patient population, to determine predictors for active use of motorized vehicles, and to compare the results with data from the general population in the respective region. (31)

They interviewed 150 participants with schizophrenia or schizoaffective disorder, 66 in-patients and 84 out-patients, in different types of out-patient services.

These authors found that 32.7% reported having been involved in a road accident even though they had driven considerably less in time and distances than the general population.

Quite clearly the driving of motorized vehicles may be dangerous due to positive, negative, and cognitive symptoms, side effects of antipsychotic drugs and concomitant substance abuse.

However participation of people with schizophrenia in individual mobility is a vital aspect of inclusion according to the UN convention of human rights of persons with disabilities.

How do we save lives and reduce serious trauma injuries attributable to motor vehicle accidents for patients on sedating antipsychotics?

Currently heavily sedating anti-psychotic drugs contribute over $US 2 Billion in annual sales for the US market.

However, no company as yet has undertaken the mandatory phase 3 clinical research that would lead to a label addition confirming superior safety for their product.

This is despite the fact we possess very sensitive technologies such as car following tests, car simulators and laboratory equipment that would achieve this result.

Furthermore, there are numerous minimally sedating oral, injectable and pipeline drugs like Aripiprazole,Cariprazine, Brexpiprazole, Pimavanserin, Invega Trinza, Abilify Maintena, Aristada, and RP5063 that are very likely to obtain this favourable label addition.

Conclusion

The earlier these phase 3 studies are undertaken, the sooner we are able to significantly reduce deaths and serious trauma injuries for patients who are on these heavily sedating antipsychotics.

References

(1) Diseases and Conditions. Schizophrenia https://www.mayoclinic.org/diseases-conditions/schizophrenia/basics/definition/con-2002107

(2) Symptoms. https://www.mayoclinic.org/diseases-conditions/schizophrenia/basics/symptoms/con-20021077

(3) Causes. https://www.mayoclinic.org/diseases-conditions/schizophrenia/basics/causes/con-20021077

(4) Risk factors. https://www.mayoclinic.org/diseases-conditions/schizophrenia/basics/risk-factors/con-20021077

(5) Complications. https://www.mayoclinic.org/diseases-conditions/schizophrenia/basics/complications/con-20021077

(6) Tests and diagnosis. https://www.mayoclinic.org/diseases-conditions/schizophrenia/basics/tests-diagnosis/con-20021077

(7) Treatments and drugs. https://www.mayoclinic.org/diseases-conditions/schizophrenia/basics/treatment/con-20021077

(8) Prevention. https://www.mayoclinic.org/diseases-conditions/schizophrenia/basics/prevention/con-20021077

(9) World Health Organization. https://www.who.int/mental_health/management/schizophrenia/en/

(10) John J McGrath. Variations in the Incidence of Schizophrenia: Data Versus Dogma. Schizophrenia Bulletin vol. 32 no. 1 pp. 195–197, 2006 doi:10.1093/schbul/sbi052 Advance Access publication on August 31, 2005

(11) McGrath J, Saha S, Welham J, El Saadi O, MacCauley C, Chant D. A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology. BMC Med 2004;2(1):13

(12) Aleman A, Kahn RS, Selten JP. Sex differences in the risk of schizophrenia: evidence from meta-analysis. Arch Gen Psychiat 2003;60(6):565–571

(13) McGrath J, Saari K, Hakko H, et al. Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth-cohort study. Schizophr Res 2004; 67(2–3): 237–245.

(14) Cantor-Graae E, Selten JP. Schizophrenia and migration: a meta-analysis and review. Am J Psychiat 2005;162(1):12–2

(15) Wylie KR, Thompson DJ, Wildqust HJ. Effects of depot neuroleptics on driving performance in chronic schizophrenic patients. J Neurol Neurosurg Psychiatry.1993 Aug; 56(8):910-3.

(16) Grabe HJ, Wolf T, Gr?tz S, Laux G. The influence of clozapine and typical neuroleptics on information processing of the central nervous system under clinical conditions in schizophrenic disorders: implications for fitness to drive. 1999 Nov; 40(4):196-201.

(17) Palmer BW, Heaton RK, Gladsjo JA, Evans JD, Patterson TL, Golshan S, Jeste DV. Heterogeneity in functional status among older outpatients with schizophrenia: employment history, living situation, and driving. Schizophr Res.2002 Jun 1; 55(3):205-15.

(18) Kagerer S, Winter C, M?ller HJ, Soyka M. Effects of haloperidol and atypical neuroleptics on psychomotor performance and driving ability in schizophrenic patients.Results from an experimental study. Neuropsychobiology 2003; 47 (4):212-8.

(19) Brunnauer A, Laux G, Geiger E, M?ller HJ. The impact of antipsychotics on psychomotor performance with regards to car driving skills. J Clin Psychopharmacol. 2004 Apr; 24(2):155-60.

(20) Soyka M, Winter C, Kagerer S, Brunnauer M, Laux G, M?ller HJ. Effects of haloperidol and risperidone on psychomotor performance relevant to driving ability in schizophrenic patients compared to healthy controls. J Psychiatr Res.2005 Jan; 39(1):101-8.

(21) Marshal SC. The role of reduced fitness to drive due to medical impairments in explaining crashes involving older drivers. Traffic Inj Prev.2008 Aug; 9(4):291-8. doi: 10.1080/15389580801895244.

(22) Alexander Brunnauer, Gerd Laux and Sarah Zwick. 2009. Driving simulator performance and psychomotor functions of schizophrenic patients treated with antipsychotics. Eur.Arch. Psychiatry .Clin. Neurosci; 483-489

(23) Brunnauer A, Laux G. Driving ability under sertindole. 2012 Mar; 45(2):47-50. doi: 10.1055/s-0031-1287781. Epub 2011 Oct 11.

(24) Gallhofer , P. Jaanson, A. Mittoux, P. Tangh ? j, S. Lis, S. Krieger. Course of Recovery of Cognitive Impairment in Patients with Schizophrenia: A Randomised Double Blind Study Comparing Sertindole and Haloperidol. Pharmacopsychiatry 2007; 40: 1 – 12

(25) Lipskaya-Velikovsky L, Kotler M, Weiss P, Kaspi M, Gamzo S, Ratzon N. Car driving in schizophrenia: can visual memory and organization make a difference? Disabil Rehabil.2013 Sep; 35(20):1734-9. doi: 10.3109/09638288.2012.753116. Epub 2013 Jan 25.

(26) Laux G, Brunnauer A. Driving ability with affective disorders and under psychotropic drugs. 2014 Jul; 85(7):822-8. doi: 10.1007/s00115-013-3994-2.

(27) Soyka M, Dittert S, Kagerer-Volk S, Soyka M. Driving ability with alcohol and drug dependence and schizophrenia. 2014 Jul; 85(7):816-21. doi: 10.1007/s00115-013-3993-3.

(28) Rethink Mental Illness. Factsheet. Driving_And_Mental_Ilness_Factsheet.pdf. page 5

(29) Segmiller FM, Buschert V, Laux G3, Nedopil N, Palm U, Furjanic K, Zwanzger P, Brunnauer A. Driving skills in unmedicated first- and recurrent-episode schizophrenic patients. Eur Arch Psychiatry Clin Neurosci.2015 Oct 25. [Epub ahead of print]

(30) Leroy A, Morse MM, for the US Department of Transportation/National Highway Traffic Safety Administration. Exploratory study of the relationship between multiple medications and vehicle crashes: analysis of databases. Washington, DC: U.S.DOT/NHTSA; 2008: Publication DTNH22-02-C-05075

(31) Steinert T, Veit F, Schmid P, Jacob Snellgrove B, Borbé R. Participating in mobility: People with schizophrenia driving motorized vehicles. Psychiatry Res.2015 Aug 30; 228(3):719-23. doi: 10.1016/j.psychres.2015.05.034. Epub 2015 Jun 6.

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