Studies which I made on myself and a group of normal subjects show that with ordinary therapeutic doses there is little or no deleterious effect on the intellectual performance.  Seven of my depressive patients were studied by means of psychometric tests selected form the revised Terman-Merrill scale.  The results suggest that memory work calling for the use of reasoning powers and logical integration of facts suffers slightly after taking the drug, but that the more mechanical memory is unimpaired and may actually show a slight improvement.  In normal subjects engaged in work of an intellectual nature there appears to be little or no falling-off of intellectual capacity, the only inconvenience experienced from the drug being the slight distractibility and pressure of ideas, and the tendency to day-dreaming and wandering of the stream of thought in the later stages. 


Therapeutic Trials in Depressive Patients
  
Therapeutic trials were made with the drug in a series of 50 patients showing the thalamic dysfunction syndrome, including cases of both the dysoxic (depressive-psychotic) and the neurotic-depressive types.  The dosages employed varied from 15 to 90 mg., the drug being administered in all cases immediately on rising in the morning before a meal was taken.  Suggestion and other psychological factors which might have vitiated the results were eliminated by substituting, without the patient's knowledge on certain days, inert control tablets of exactly similar appearance to those containing the synhexyl.
  
The general effects were found to be qualitatively similar to those in the 'normal' subject, except that a considerably higher average dose was required to produce improvement of the depressive symptoms.  It was found that the dysphoria itself was ameliorated to a much greater degree than the other symptoms (obsession thoughts, pains, paraesthesias, etc.) ; these features, although themselves little affected were rendered less distressing and obtrusive to the patient by the action of the drug.
  
Of the 50 cases tested 36 showed a definite improvement in affective reaction, while 14 were unaffected or made worse.  Twenty-seven of the series were neurotic-depressive, 20 of whom showed improvement ; of these 27, 12 were typical chronic mental hospital cases, of whom 9 benefited from the drug.  Of these 12, 9 had previously been treated with electro-anoxia with no improvement, and 3 had been subjected to prefrontal leucotomy with no response.  The remaining 23 patients were cases of dysoxic depression, of whom all but 4 were chronic institutionalized patients with mild symptoms of dysphoric type.  Four of the 23 had previously received electro-anoxia with temporary improvement only ; of these four, two responded favorably to the drug.
  
Of the whole series, 16 patients showed associated organic diseases as follows :  gross bony deformity, 2 ; pulmonary tuberculosis, 2 ; cardiovascular disease, 5 ; senile changes, 4 ; malignant disease, 1 ; organic nervous disease, 1 ; thyrotoxicosis, 1.  No untoward side-effects from the synhexyl were noted in any of these cases.  Untoward effects were noted in 5 of the neurotic-depressive cases ; these included tachycardia, slight dizziness, loss of concentration, drowsiness, and mild degrees of impairment of the intellectual performance.
  
The criteria for a positive response were taken as the following: amelioration of mood, as shown subjectively by the patients' own statements and objectively by clinical evidence of diminution of retardation, anxiety, and inward preoccupation ; increased zest for and interest in work and occupation ; and increased psychotherapeutic rapport.  The effect of the drug on obsession and depressive ideas and pains and paraesthesias of central origin was also noted.  The nursing staff were carefully instructed to note during the tests any changes in the general behavior and demeanor of the patients while receiving the drug.  The results with synhexyl were then compared with the response to inert control tablets.
  
Of the dysoxic patients those in the chronic stationary phase of their disease made the best response.  Three dysoxics in the acute depressive phase either showed no response or were actually made worse when synhexyl was given in doses of 60-90 mg.
  
Of the neurotic group, the quiet apathetic type with depression and general asthenia appeared to do best ; this type required the smallest dosage to effect improvement --15 mg.  The tense and over-anxious type also showed a good response but tended to require a rather higher dosage -- 30-60 mg.  The anxiety cases with multiple pains and paraesthesias were found to improve considerably as regards the dysphoria, but the drug seemed to have little effect on the actual sensory features.  Six of the neurotic cases were severe examples of the obsessive-ruminative type, only one of whom failed to improve with the drug.
  
Neurotic-depressive cases showing a negative response included psychopathic personality with dysphoric features (two cases) and acute hysterical grief reaction with pseudohallucinosis (one case.)