Jan Wålinder

LITHIUM TREATMENT ON ATYPICAL INDICATION

As regards the duration of the observation times, our experience of lithium is in no way comparable with that of our Danish colleagues. To a certain extent, however, we have used the substance on indications other than those usually motivating this therapy, and it is with the experience gained in this connection that this preliminary report deals. T h e astonishingly good results we attained by applying the treatment to manic states led us perhaps into a certain ’lithiomania’, and we began to try out the drug on various severe pathological states that had proved resistant to other measures. Our criterion for considering a case to be treated on atypical indication is the following: the existing picture has not permitted of the diagnosis manic-depressive psychosis before the therapeutic experiment. In several cases a positive result of the lithium therapy has led us to suspect that this diagnosis had as a matter of fact been correct. We shall revert tc, the question of such a diagnosis ex juvantibus after the case histories. The number of cases treated on atypical indication amounts to 27, 15 women and 12 men. In 9 of these cases we observed no effect whatsoever. These formed a group of patients with very varying symptomatology and we shall not at this stage give the case histories. There was a phasic course in 4 of the cases. The group is of course interesting as comparative material, but it is as yet so small that we refrain for the time being from making comparisons. There remain 18 atypical cases in which what we considered a distinct effect was observable, sometimes modest, sometimes very striking. We give a brief account of the 1 8 cases, though in the first and last we go into somewhat greater detail as they are particularly illustrative.

Monoamines, BDNF, IL-6 and corticosterone in CSF in patients with Parkinson’s disease and major depression

The biochemical basis of major depression (MD) in Parkinson’s disease (PD) is largely unknown. To increase our understanding of MD in PD patients, the levels of monoamine metabolites (HVA, 5-HIAA and MHPG), BDNF, orexin-A, IL-6 and corticosterone were examined in cerebrospinal fluid. The analyses were performed in MD patients with (nxa0=xa011) and without (nxa0=xa012) PD at baseline and after 12xa0weeks’ of treatment with the antidepressant citalopram, and in patients with solely PD (nxa0=xa014) at baseline and after 12xa0weeks. The major findings were that PD patients with MD had significantly lower baseline levels of MHPG, corticosterone and IL-6 when compared to patients with solely MD. In response to citalopram treatment, patients with solely MD exhibited an expected decrease in 5-HIAA and MHPG levels which was not found in PD patients with MD. Moreover, the levels of BDNF and IL-6 were lower in PD patients with MD compared with patients with solely MD after treatment with citalopram. Thus, the biochemical basis and the response to citalopram differ between PD patients with MD and patients with solely MD.

5-HT reuptake inhibitors plus tryptophan in endogenous depression

In a previous double‐blind, 3‐week study we compared the effect of clomipramine + placebo with clomipramine + tryptophan in 24 patients with endogenous depression. The patients in the latter group showed a significantly more rapid improvement than those in the former group, especially with regard to the depression‐anxiety cluster of symptoms.

HMPAO SPECT in Parkinson’s disease (PD) with major depression (MD) before and after antidepressant treatment

Previously we suggested that major depression (MD) in Parkinson’s disease (PD) could be an indication of a more advanced and widespread neurodegenerative process, as PD symptoms were more severe in those with depression. We also found a different antidepressant response with SSRI medication in PD patients with depression compared to depressed patients without PD. This indicates diverse underlying pathophysiological mechanisms. Investigations using single-photon emission computed tomography (SPECT), measuring regional cerebral blood flow (rCBF), may contribute to enlighten the neurobiological substrates linked to depressive symptoms. SPECT was performed in order to compare rCBF in MD patients with and without PD. The study included 11 MD patients with PD, 14 non-depressed PD patients and 12 MD patients without PD. All patients were followed for 12xa0weeks with repeated evaluation of depressive as well as PD symptoms. Anti-Parkinsonian treatment remained unchanged during the study. Antidepressant treatment with SSRI (citalopram) was given to all patients with MD. SPECT was performed before and after 12xa0weeks of antidepressant treatment. rCBF was found to differ between PD patients with and without MD, as well as between MD patients with and without PD, both at baseline and concerning the response to treatment with SSRI (citalopram). In patients with PD the rCBF was found to be decreased in preoccipital and occipital regions, a finding more common when PD was combined with MD. In summary, larger cortical areas were found to be involved in depressed PD patients, both with hyperactivity (reciprocal to basal degeneration in PD and maybe dopaminergic treatment) and with hypoactivity (probably due to organic lesions leading to hypoperfusion). These observations support our hypothesis that PD combined with MD is an expression of a more advanced and widespread neurodegenerative disorder.

No inhibition by Li+ of thyroxine monodeiodination to 3,5,3′-triiodothyronine and 3,3′,5′-triiodothyronine (reverse triiodothyronine)

The possibility that lithium affects the conversion of thyroxine to 3,5,3-triiodothyronine and 3,3,5-triiodothyronine (reverse triiodothyronine) was studied by measurement of the serum concentractions of these parameters in five patients during the first week of lithium therapy. In three patients there was a decrease in serum thyroxine concentration and a slightly less pronounced decrease in that of serum 3,5,3-triiodothyronine. In two patients, who also received L-tryptophan or flupentixol, no change was noted in the concentrations of these compounds. There was no increase in serum 3,3,5-triiodothyronine concentration in any of the patients. No systematic change was found in the serum concentrations of thyrotropin or unsaturated thyroid-hormone binding proteins. The results obtained do not support the contention that lithium should inhibit the monodeiodenation of thyroxine to its active and inactive metabolites.

Electroconvulsive therapy and receptor sensitivity

Administration to rats of one electroconvulsion daily for seven days (ECS × VII) resulted in enhanced behavioural responses to dopamine (DA) agonists and enhanced growth hormone (GH) secretion after treatment with reserpine followed by the DA agonist apomorphine and the noradrenaline (NA) agonist clonidine. The GH response to reserpine followed by clonidine alone was unaffected by pretreatment with ECS × VII. The enhancements, which in animals persist for at least ten days, indicate increased responsiveness in DA sensitive structures. Subsequent investigations in other laboratories have found no changes in either DA‐binding sites or in the DA activated adenylate cyclase system after repeated ECS. The treatment must therefore be assumed to engage structures connected to the DA receptors rather than the receptors themselves. The hGH response was studied in depressed patients before and after electroconvulsive therapy (ECT) and twice also in a control group, where the subjects received no treatment between the two investigations. ECT induced no unitary change in hGH responses. The intra‐individual variation was however significantly greater in the ECT treated patients than in the controls. Eight parkinsonian patients with partial therapy resistence to L‐DOPA were administered ECT during maintenance of their L‐DOPA therapy. Six out of 8 patients improved with respect to their extrapyramidal symptoms. The improvement after ECT was significantly correlated to the duration of the L‐DOPA therapy but not to the degree of mental depression. The results indicate that changes, related to DA receptors, also develop when ECT is administered clinically.

Tryptophan malabsorption in dementia. Improvement in certain cases after tryptophan therapy as indicated by mental behaviour and blood analysis

Twenty‐four senile dementia patients in the age range 65–85 years were subjected to a new sensitive tryptophan loading test: Dopa‐Tryptophan loading (“Dop‐Try loading”) in order to determine whether Try malabsorption occurs in senile dementia and if so how frequent this is. For comparison the same loading test was performed on 23 subjects in the same age grouping but with normal mental function. The differences in Try absorption were statistically analyzed and this revealed that absorption was less effective in the senile dementia group.

Potentiation of the effect of antidepressant drugs by tryptophan.

Extensive pharmacological and clinical investigations have led to the suggestion ~hat monoamines, i.e. catecholamines and 5-hydroxytryptamine (5-HT) may be mvolved in depression. The first enzyme involved in the synthesis of 5-HT, i.e. tryptophan hydroxylase, is not fully saturated with its substrate tryptophan, and thus administration of this precursor will result in an increased synthesis. Clinical reports on the efficacy of tryptophan treatment in depressive disorders are, however, conflicting. A possible explanation for the ambiguous results may be that the increase in 5-HT synthesis induced by tryptophan will largely be neutralised by increased intracellular deamination, the net result thus being no marked increase in 5-HT concentration at receptor sites. In support of this hy~othesis are a few reports on the successful combination of monoamine OXidase inhibitors and tryptophan ( Coppen eta/. 1963, Pare 1963, Glassman eta/. 1969).

Parental contact in male and female transsexuals

The parental contact reported by 12 biologically male and 12 biologically female transsexuals was compared with that reported by control subjects (109 conscripts in the Swedish Army; 101 pregnant nulliparous women). Parental contact was estimated for three different periods: 1) childhood, 2) adolescence, 3) the year before investigation.

Lithium effect as aid in psychiatric diagnostics

Erik Essen-Moller (1961) in one of his works deals with the question of the classification of mental disorders. I t discusses in various sections the problems of inconsistency, of contamination, and of divergency. His deliberations lead up to a proposal of principle concerning the simultaneous use of two separate lists for the classification of mental disorders, one syndromatic and the other aetiological. The two cases we refer to in this paper offer excellent examples of the perpetual dilemma of psychiatric classification. Both cases were diagnosed with inconsistency, contamination, and considerable divergency. They seem interesting in the classification debate also from the standpoint that the syndromatic diagnoses must of necessity change from one treatment occasion to another, and also on the same treatment occasion sometimes be rather in the nature of a catalogue. In our two cases, an aetiological diagnosis was highly probable, mainly through the effect of a drug. Among the drugs that have in recent years been introduced into the therapeutic arsenal of psychiatry, lithium carbonate seems to us to be one of the most interesting. Its specific use chiefly for manic conditions and its power to prevent recurrences of mania was brought to our notice mainly through the works of Schou and Stromgren (e.g. Schou 1959, Stromgren&Schou 1964). In one of our cases,Iithium carbonate had a high potency against phobic symptoms too. In connexion with our two cases, we will discuss the diagnostic problems and the hypothetical possibility of a diagnosis ex juvantibus.