[Hypericum and phototherapy]. / Hypericum und Lichttherapie.

A sunlight deficiency, as is experienced at our latitude in winter, induces a seasonal affective disorder (SAD) or winter depression in some people. First line of treatment of this form of depression is bright-light therapy, as a type of substitution therapy. SAD is treated with similar success using antidepressant drugs like hypericum (St. John's wort). Phototherapy also has an antidepressive effect on non-seasonal depressions, albeit not quite as pronounced. When using phototherapy light is transformed into electric impulses in the retina. These impulses are transmitted to the hypothalamus and the central nervous structures controlling metabolism, hormones and the circadian rhythms. These processes are governed by very complex regulatory mechanisms. Feedback loop mechanisms induce constant adaptation of the photosensitivity of the retinal photoreceptors while also controlling the central nervous structures. New findings on the interaction and interweaving of depression, light, metabolism, hormones and circadian rhythms support the following hypothesis: The photodynamic impact of hypericum magnifies the effect of normal light, as if the patient were subject to continuous light therapy. The photosensitizing effect of hypericum is thus not only of interest as an undesirable side-effect but also for its therapeutic effects.

Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine.

In a randomised double-blind comparative trial, the antidepressant efficacy of a daily dose of 800 mg of the St. John's wort extract LoHyp-57 (dry extract of St. John's wort, drug extrakt ratio 5-7:1, solvent, ethanol 60% [w/w]) was shown to be equivalent to that of 20 mg fluoxetine (CAS 54910-89-3) in elderly patients with mild or moderate depressive episodes according to ICD 10 (International Statistical Classification of Diseases and Related Health Problems). Treatment was given for six weeks. 149 out-patients (129 females and 20 males) were included in the intention-to-treat analysis. 72 of these patients were assigned to the ICD 10 diagnostic criterion F32.0 (mild depressive episode), while 77 patients were suffering from moderate depressive episodes, corresponding to F32.1. The principal target criterion was the patient's global score on the HAMILTON Depression Scale (items 1-17). During the six-week course of treatment with LoHyp-57, the HAMILTON global score fell from 16.60 points at entry to 7.91 points, and in the fluoxetine sample it fell from 17.18 to 8.11 points. In the group of patients with mild depressive episodes, the score showed a mean fall from 14.21 to 6.21 points on LoHyp-57, and from 15.21 to 7.46 points on fluoxetine. In patients with moderate depressive episodes, the score showed a mean fall from 18.73 to 9.43 points on LoHyp-57 and from 19.10 to 8.75 points on fluoxetine. The efficacy of both medications was found to be equivalent both in mild and moderate depressive episodes. Both treatment groups showed adverse drug reactions (ADRs). Twelve ADRs with a possible relationship to the study medication were reported during treatment with LoHyp-57. Six patients were prematurely withdrawn from treatment with the study medication for this reason. On fluoxetine 17 ADRs occurred with a possible relationship to the study medication. These led to abandonment of treatment and therefore premature withdrawal from the study in 8 cases.

[Treatment of depressive symptoms with a high concentration hypericum preparation. A multicenter placebo-controlled double-blind study]. / Behandlung depressiver Verstimmungen mit einem hochkonzentrierten Hypericumpräparat.

In a multicenter, placebo-controlled double-blind trial, the effect on depression (ICD 10 F 32.1) of treatment with an innovative highly concentrated hypericum preparation was investigated. The study contained 97 outpatients who received 100 to 120 mg of the hypericum extract bid. The course of the illness was assessed with the Hamilton Depression Scale (HAMD), the von Zerssen Depressivity Scale (D-S) and the Clinical Global Impression Scale (CGIS). Treatment resulted in an appreciable improvement in the symptoms of depression, and the 70% response rate (n = 43), corresponded to that of chemical antidepressants. The preparation also showed an anxiolytic effect. The substance was extremely well tolerated, and no side-effects were reported by any of the patients.

Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind study.

A randomized, double-blind study examining the effectiveness and tolerance of a standardized hypericum preparation when compared to maprotiline was performed in a group of 102 patients with depression, in accordance with ICD-10, F 32.1. The study was conducted in the offices of neurology and psychiatry specialists. The patients received, over a period of 4 weeks, either 3 x 300 mg of the hypericum extract or 3 x 25 mg maprotiline pills of identical appearance. Effectiveness was determined using the Hamilton Depression Scale (HAMD), the Depression Scale according to von Zerssen (D-S), and the Clinical Global Impression Scale (CGI). The total score of the HAMD scale dropped during the 4 weeks of therapy in both treatment groups by about 50%. The mean values of the D-S scale and the CGI scale showed similar results, and after 4 weeks of therapy, no significant differences in either treatment group were noticed. The onset of the effects occurred up to the second week of treatment, but were observed earlier with maprotiline than with the hypericum extract. On the other hand, maprotiline treatment resulted in more cases of tiredness, mouth dryness, and heart complaints.

Clinical investigation of the antidepressant effectiveness of hypericum.

To date, 25 controlled therapy studies have investigated the antidepressive effectiveness of hypericum extracts. A total of 1592 treatment cases have been included. The dosage was typically 300 to 900 mg total extract daily; the therapy duration was 2 to 6 weeks. Fifteen studies were performed comparing hypericum extracts with placebo, 10 studies as comparative studies. This paper presents an overview of their results.

Placebo-controlled double-blind study examining the effectiveness of an hypericum preparation in 105 mildly depressed patients.

One hundred and five outpatients with mild depressions of short duration were treated in a double-blind study with either 3 x 300 mg hypericum extract or placebo. The therapy phase was 4 weeks. The effectiveness was judged according to the Hamilton Depression Scale after 2 and 4 weeks. The values of the mean basic score in these periods fell from 15.8 to 9.6 or 7.2 in the active group, and in the placebo group, from 15.8 to 12.3 and 11.3. The differences between active and placebo groups were statistically significant with P < .05 and P < .01 achieved after 2 and 4 weeks, respectively. In the active group, 28 of 42 patients (67%) and, in the placebo group, 13 of 47 patients (28%) responded to treatment. Notable side effects were not found.

Treatment of mild/moderate depressions with Hypericum.

105 out-patients with neurotic depressions or depressive irritations of short duration were treated in a double-blind study either with 3 × 300 mg Hypericum extract or placebo. The therapy phase was four weeks. The effectiveness was judged according to the Hamilton Depression Scale after two and four weeks. The values of the mean basic score fell in these periods in the active group from 15.81 to 9.64 and 7.17 and in the placebo group from 15.83 to 12.28 and 11.30. The difference between active and placebo groups were statistically significant with p < 0.05 and p < 0.01 achieved after 2 and 4 weeks respectively. In the active group 28 of 42 patients (67 %) and, in the placebo group, 13 of 47 patients (28 %) could be defined as responding to treatment. Notable side effects were not found.

[Disorders of the neurotransmitter system in multiple sclerosis--possibilities for a therapeutic approach?]. / Störungen im Neuro- Transmitter-system bei Multipler Sklerose--Möglichkeiten eines therapeutischen Ansatzes?

The type and extent of neurological deficits in multiple sclerosis depends on the localisation and size of the lesion and the type of neuropathological pattern of the lesion. The elective demyelinating process (loss of myeline sheath without axonal damage) brings, about a showing and faulty conduction of impulses and thereby a disturbed processing of information. It can finally come to a total (functional, reversible) conduction blockage. Additionally also disturbances in the synaptic transmission may be involved. The occurrence and extent of these disturbances in conduction and transmission depend on definite paristatic factors. Our presented concepts of the "therapeutic model" based on pathophysiological investigations in multiple sclerosis show the tendency towards a "marked symptomatic therapy", which does not however, influence the basis of the disease processes, but rather represents an extremely helpful suppression of symptoms for the patients concerned.

[Therapy of multiple sclerosis]. / Zur Therapie der Multiplen Sklerose.

The routine therapy of multiple sclerosis (MS) in world-wide use today is comprised of four measures: Antiinflammatory and antiedematous treatment with ACTH or Synacthen, respectively, and corticosteroids: only during acute episodes. - High dosage, short duration, no long-term therapy. Immunosuppression with azathioprine (Imurek): Due to the relatively high risk only to use in malignant courses (frequent and severe bouts). Basic therapy with unsaturated fatty acids (sunflower oil, Naudicelle). Influencing circumscribed target symptoms (spasticity, micturition difficulties, constipation, etc.). In addition, physiotherapeutic, psychagogic and, if necessary, nursing and social measures are included. More than a decade's experience with ultrasound therapy of the lymphatic ring as developed by Selzer in over 300 MS-patients gives the impression of a reduction in bout frequency and severity. A statistical evaluation of therapeutic efficiency has so far been impossible for well-known disease-specific reasons, which hold true for all MS-treatment methods. Great practical importance within a foreseeable space of time may be reached by efforts to influence disturbance in nerve conduction and synaptic transmission as specifically caused by the demyelination process. The successful medicinal deceleration of sodium inactivation, inhibition of potassium activation and extension of the action potential, as well as specifically influencing the neurotransmitters responsible for the disturbed synaptic transmission could lead to a total recovery or improvement of dysfunction in a great many cases. Such a "global symptomatic therapy" might indeed not change the course of disease, but bring about great progress to the patient.