Digit Symbol Substitution Test

Digital Symbol Substitution Test. A subtest of the Wechsler Adult Intelligence Scale (WAIS), the Digital Symbol Substitution test measures sensory-motor integration and learning relationships of symbols. It has been used in many psychophar-macological studies. Subjects are given different forms of this test at each session. The test requires the patient to match as many of 100 symbols to their respective numerals, found in a code key, as possible within 60 seconds. 

Opioids are sedating and cause a reduction in processing speed in clinical populations (e.g.. Digit Symbol Substitution Test) (Wood et al. 1998). However, a study in healthy subjects did not confirm these effects on digit substitution (Walker and Zacny 1998). Improvements are seen in choice reaction time after morphine administration (Hanks et al. 1995). Deficits have been reported in early-stage visual processing (O Neill et al. 1995 Hanks et al. 1995). By comparison, morphine s cognitive effects are lesser than those of lorazepam, but milder than hydromorphone (Rapp et al. 1996 Hanks et al. 1995). 

Digit symbol substitution tests (DSST) allocation of given symbols to numbers. Contains short-term memory component... 

With regard to modafinil s effects on task performance, the drug appears to have minimal impact on simple psychomotor tests (at least in untreated narcoleptics), whereas there are tendencies toward improvement in more complex tasks requiring concentration, dexterity, and the coordination of cognitive and motor resources (215). In non-sleep-deprived normals, it has been determined that 200 mg had no effect on the performance of a digit symbol substitution test despite improved EEG activation (measured by theta/alpha ratios) for up to 6 hr postdose (219). 

Figure 7 Mean changes over baseline in scores on the DSST during each of the five trials, as discussed in the text and in Fig. 4. Abbreviations DSST, digit-symbol substitution test TRZ, triazolam CLAR, clarithromycin ERY, erythromycin AZ, azithromycin PL, placebo. Source From Ref. 77.

Greenblatt DJ, Gan L, Harmatz JS, et al. Kinetics and dynamics of single-dose triazolam electroencephalography compared to the digit-symbol substitution test. Br J Clin Pharmacol 2005 60 244-248. 

In a randomized, double-blind, placebo-controlled, crossover study in 10 healthy men, itraconazole 200 mg/day for 4 days significantly altered the pharmacokinetics of a single dose of brotizolam 0.5 mg it reduced the apparent oral clearance four-fold, increased the AUC0 24h more than two-fold, and prolonged the half-life five-fold (6). The digit symbol substitution test and sleepiness were significantly altered as a result. 

In a double-blind, placebo-controlled study of sex differences in the effects of lorazepam in trained social drinkers, lorazepam substituted for alcohol equally in both sexes and increased associated scores for light-headedness (14). The women had much greater performance impairment in a digital symbol substitution test after lorazepam than the men. These results suggest that the stimulus and cognitive effects of benzodiazepine receptor agonists are modulated by different brain mechanisms. 

In a double-blind, crossover, randomized, placebo-controlled study in 22 healthy volunteers, single doses of zolpidem 10 mg and triazolam 0.25 mg had no effect on the enhanced non-word recall observed after sleep or on improvement in the performance of a digit symbol substitution test in subjects who slept (30). The authors concluded that the hypnotics did not interfere with nocturnal sleep-induced improvement in memory. 

The effects of loratadine 10, 20, and 40 mg on tests of visnomotor coordination, dynamic visnal acnity, shortterm memory, digit symbol snbstitntion, and snbjective assessments of mood have been stndied (68). Triprohdine was used as an active control and impaired performance on all the tasks presented. Loratadine 40 mg caused a significant impairment of the Digit Symbol Substitution Test and the Dynamic Visual Acuity Test, but the 10 and 20 mg doses were without effect. Loratadine did not affect objective sleepiness, as measured by Multiple Sleep Latency Test (69). In other studies of loratadine in the normal 10 mg dose the sedation rate was no different from placebo (SEDA-12, 143) (SEDA-14, 136). 

FIGURE 22.1 This figure is an example of a Digit Symbol Substitution Test (DSST). Typical tests require a subject to substitute up to 90 symbols using the key directly above the test table. The key performance measures are speed and accuracy. The DSST is a measure of psychomotor performance, attention, and ability to remember and operate on complex symbols. It is one of the first tests to show decline with the onset of dementia, and in some instances it may exhibit decline even before dementia is clinically manifest. Norms are based on sex and age. 

A slight but statistically significant t drowsiness due to a 1.5-fbld t in AUC and a 1,3-fold t in maximum concentration with triazolam that was accompanied by a t in reaching peak effects (from f. 6 to 2.5 hours). There is t AUC, maximum concentration and T max of quazepam and its active metabolite 2-oxoquazepam. No change is seen in psychomotor function with alprazolam, while with diazepam there was t maximum concentration. With midazolam, there was minor t reaction time (and minor t digital symbol substitution test results)... 

Ketoconazole. A study in 12 healthy subjects found that following three 200-mg doses of ketoconazole given every 12 hours, the AUC of zolpidem 5 mg was increased 1.7-fold and the subjects were more sedated, as shown by the digit symbol substitution test."... 

A pharmaeokinetie study in 10 healthy subjects found that rifampicin 600 mg daily for 5 days reduced the AUC of a single 15-mg oral dose of midazolam by 96%, and reduced the half-life by almost two-thirds. The psychomotor effects of the midazolam (as measured by the digit symbol substitution test, Maddox wing test, postural sway and drowsiness) were almost totally lost. ... 

Acute psychomotor effects of cannabis administration include decreased postural balance (48,49), increased body sway (due to impaired equilibrium) (50), and increased tremor. Effects on simple and complex reaction time tasks are mixed, with some studies reporting impaired performance (51,52) and others showing no effect (50,53). Acute cannabis administration can also impair performance on the digit symbol substitution test (DSST) (9,13,49),... 

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