Case 1.--A woman aged 60, with a history of recurrent attacks of depression over the last three years.  On examination she was tense, agitated, acutely apprehensive, restless and excitable at times, and expressed selfdeprecatory ideas of being wicked and worthless.  Orientation and memory were unaffected and insight and judgment were moderately good, but she cooperated poorly in examination owing to her constant preoccupation with delusions of unworthiness.  Physical findings were negative.  She received electric convulsion treatment with no real improvement, remaining in the agitated state described above.  After receiving 30 to 45 mg. of synhexyl daily she showed marked improvement ; she said she felt brighter, and the agitation and tension were definitely diminished.  Although the ideas of unworthiness persisted in mild degree, these were much less obtrusive and distressing.  No untoward symptoms were noted, and response to control tablets was negative.
Case 2.--A man aged 65.  The history was very incomplete, but it appeared that he was originally admitted in 1938, following the sudden onset of an acute depressive-confusional state with paranoid and possibly hallucinatory features.  On examination he was depressed, apathetic, hypochondriac and full of ideas of visceral dysfunction, totally lacking in initiative, but well behaved and clean in habits.  There were no signs of hallucinosis or paranoid features, but he showed a mild degree of personality deterioration, being at times facile, rambling, and irrelevant in conversation.  Physical investigations were negative.  He responded fairly well to 30 mg. of synhexyl daily, becoming brighter, less querulous and preoccupied with his aches and pains, and stated that he felt more cheerful and energetic.  The symptoms of cortical deterioration and institutionalization were, however, unchanged.  No side-effects were apparent during the period of medication.
Case 3.--A woman aged 67 with a history of recurrent depressive attacks since 1936, and two previous admissions to hospital for acute depression.  Examination showed her to be depressed, solitary, and lacking in interest and initiative.  She complained of obstinate insomnia, and required constant nocturnal sedation.  She displayed no evidence of delusions and hallucinations, but tended to be mildly retarded and sat about aimlessly all day in the ward.  Physical examination revealed a slow-growing breast carcinoma, for which operation had been considered inadvisable.  She had previously received E.C.T. with little or no improvement.  She received synhexyl in a dosage of 15 mg. daily with considerable subjective and objective improvement.  She felt brighter, more alert and cheerful, and showed increased initiative and spontaneous activity.  Side-effects were absent, and administration of control tablets failed to reproduce the synhexyl effect.
Case 4.--A woman aged 45.  She had a history of the onset, three months previously, of acute depression with agitation, ideas of bodily disease, and delusions of sin and unworthiness, apparently precipitated by an unhappy home environment.  When she was first seen, the acute phase of the illness had subsided and she talked rationally, showing considerable insight.  She complained of mild depression, fatigability, and insomnia, with a variety of vague stomach pains and soreness and pains in her throat.  She insisted that she had "swollen and painful glands" in her neck ; but examination showed only a small palpable cervical gland on the right side, the throat and tonsils being normal.  She also complained of feelings of "being all trembly inside."  Delusions of unworthiness were not in evidence.  She was a small, pale, anxious-looking woman, but no signs of organic disease were present.  She was described by the nursing staff as depressed, solitary, and apathetic in habits.  The administration of 45 mg. of synhexyl produced an immediate effect ; she stated that she felt subjectively brighter and more cheerful, showed increased interest, and her hypochondriac ideas receded into the background.  Vasomotor side-effects were absent, control tests giving a negative result. 

Case 5.--A woman aged 52, with thalamic dysfunction of conversion hysteria type.  She had a history of depression for 18 months following evacuation during the flying-bomb raids and an accident to her son.  She had also had a previous depressive attack 28 years ago.  On examination she was depressed, tense, emotional, and anxious.  Her main complaints were of insomnia, inability to face up to her household duties, and a persistent neuralgic pain located under the left breast.  Physical findings were completely negative.  A few weeks previously she received seven applications of E.C.T. with slight improvement but speedy relapse.  The response to 30 mg. of synhexyl was immediate ; she lost her anxiety and depression, said she felt much brighter, and the thoracic pain became much less insistent and distressing, although not completely abolished.  Control tablets and bromide in full dosage failed to reproduce these effects.  No side-effects from the synhexyl were complained of during the period of administration.
Case 6.--A woman aged 32 with thalamic dysfunction of anxiety type.  She had a history of anxiety symptoms 18 months previously, and partial remission but recurrence four months before admission, at which time she had gone to live with and look after her invalid mother.  On examination she was a superior and intelligent type of woman, outwardly cheerful in manner, but actually tense, anxious, and mildly depressed.  She complained of insomnia, intermittent panic sensations with palpitation, and acute feelings of inner tension and "shivering sensations," and loss of concentration.  Physical findings were negative, and no signs suggestive of thyroid hyperfunction were evident.  The symptoms failed to respond to bromide therapy and psychotherapy.  She responded well to synhexyl in doses of 30 mg. daily, the anxiety attacks and dysphoria being completely abolished.  She stated that she felt much brighter, more confident, and was no longer apprehensive of the anxiety attacks.  Her symptoms recurred on changing over to control tablets or discontinuing the synhexyl.
Of these six cases, selected at random from my series, the first four were dysoxic (psychotic-depressive) cases and the last two examples of simple thalamic dysfunction (neurotic depression).  The four dysoxic cases were all patients who had passed through the acute phase of their illness and who presented as the principal symptom a residual dysphoria of chronic and intractable type.  Of these four, one (Case 2) showed some degree of personality deterioration.  The two neurotic cases were of recent onset and in the early stages of their illness.  Of the six cases, three (Cases 1, 3, 5) had previously failed to respond satisfactorily to E.C.T.  It will be evident from this series that synhexyl is as effective in the milder forms of dysoxia as in the purely neurotic-depressive states.
As regards the mechanism of improvement, it should be pointed out that synhexyl does not effect a permanent "cure" in the same way as electro-anoxia does in typical dysoxic depressions.  The effect lasts only during the period of administration of the drug ; it is therefore a substitution therapy, like insulin treatment in diabetes or liver extract in pernicious anaemia.  The action would seem to be a combination of stimulation and depression, resulting in a general raising of the anhedonic threshold.  The principal site of action of the drug is almost certainly the thalamic centres and their cortical connections, as is the case with morphine and other powerful central analgesic drugs.

The beneficial effects of synhexyl do not appear to be adversely affected by chronicity, concomitant organic disease, or the presence of an organic brain lesion, whether pathologically or surgically induced.  There is evidence, however, that drugs of this class are ineffective in the acute dysoxic depressions, and cannot be regarded as substitutes for anoxic therapy in this form of metabolic brain disease.