Predictors of response to combined wake and light therapy in treatment-resistant inpatients with depression

ABSTRACT

There is growing evidence for combined chronotherapeutic interventions as adjunctive treatments for major depression. However, as the treatments can be demanding, we need to identify predictors of response. This study aimed to describe predictors of response, remission and deterioration in the short-term phase, as well as predictors of long-term response. The predictors investigated were gender, type of depression, severity of depression, treatment resistance, quetiapine use, general self-efficacy, educational level and positive diurnal variation. Follow-up data from 27 inpatients with moderate-to-severe depression participating in a chronotherapeutic intervention were analysed. As a supplement to standard treatment, they completed 3 wake therapy sessions in the first week, 30 min daily light treatment and sleep-time stabilisation in the entire 9-week study period. Patients had a significant decrease of depressive symptoms during the first 6 days measured by HAM-D6. At Day 6, 41% of the patients responded to the treatment and 19% fulfilled the criteria of remission. Deterioration by the end of wake therapy sessions was however not uncommon. In the short-term phase, mild degree of treatment resistance was associated with remission and low educational level associated with deterioration. Positive diurnal variation (mood best in the evening) was a predictor of both short-term and long-term response to combined wake and light therapy. Furthermore, patients with evening chronotypes (measured with morningness-eveningness score) were more responsive. Our results suggest that targeting the combined chronotherapeutic intervention at patients with positive diurnal variation and evening types is a viable option.     

Antidepressant effects of mono- and combined non-drug treatments for seasonal and non-seasonal depression

The involvement of chronobiological mechanisms in the antidepressant response to such non-drug treatments as bright light, physical exercise and sleep deprivation still remain to be clarified. We compare the efficacy of several treatment strategies for seasonal and non-seasonal depression and discuss possible the contribution of chronobiological and psychological mechanisms in antidepressant response. The therapeutic effects were tested at the medical academic hospital near Novosibirsk (55 degrees North) in 138 subjects, either with winter depression or with non-seasonal depression or without depression (n = 41, 64 and 33, respectively). One-week monotreatments were either 2-hour 2500 lux cool-white incandescent light from 14:00 (n = 9, 9, 9, respectively) or 1-hour physical exercise from 13:00 (n = 9, 9, 9, respectively). One-week combined treatments included a night of total sleep deprivation followed by either 2-hour bright light from 14:00 (n = 8, 12, 0, respectively) or 1-hour physical exercise either under ordinary room light from 13:00 (n = 0, 12, 0, respectively) or under bright light from 12:00 (n = 5, 11, 0, respectively). The results indicate that, in subjects left without antidepressant treatment for a week (n = 10, 11, and 15, respectively), the 21-item Hamilton Depression Rating Scale score did not change significantly. The beneficial effects of total sleep deprivation were similar in seasonal and non-seasonal depression. The seasonals exhibited better response to bright light compared to non-seasonals. After sleep deprivation the substantial further improvements were produced by either lighting or exercising. Compared to the patients exercising under ordinary room light, the patients exercising under bright light did not gain an additional benefit. In general, winter depression was well-treated with either exercise or light, while the most promising treatment for non-seasonal depression was physical exercise combined with sleep deprivation. Bright light or physical exercise administered in the middle of the day were not less favorable compared to the treatments in the morning hours, although it is unlikely that they considerably challenged patient's chronobiology. It was concluded that the placebo effect would account for a large portion of clinical response to open non-pharmacological treatments. Therapeutic hops and visibility of such treatments would explain their high antidepressant efficacy in comparison with pharmacological trials applying a double blind cross-over design. In particular, the excellent response of patients with winter depression to light therapy might be related to their tendency to attribute a high symbolic value to bright light and associate their bad mood with a dark season.     

Efficacy of light therapy for perinatal depression: a review

ABSTRACT: Perinatal depression is an important public health problem affecting 10-20% of childbearing women. Perinatal depression is associated with significant morbidity, and has enormous consequences for the well-being of the mother and child. Treatment of depression during the perinatal period poses a complex problem for both mother and clinician, as antidepressant treatment strategies must consider the welfare of both mother and child during pregnancy and lactation. Bright light therapy may be an attractive treatment for perinatal depression because it is low cost, home-based, and has a much lower side effect profile than pharmacotherapy. The antidepressant effects of bright light are well established, and there are several rationales for expecting that bright light might also be efficacious for perinatal depression. This review describes these rationales, summarizes the available evidence on the efficacy of bright light therapy for perinatal depression, and discusses future directions for investigation of bright light therapy as a treatment for perinatal depression.     

Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks

ObjectivesTo assess the efficacy and safety of hypericum extract (STEI 300, Steiner Arzneimittel, Berlin) compared with imipramine and placebo in patients in primary care with a current episode of moderate depression.DesignRandomised, double blind, multicentre, parallel group trial for 8 weeks.SettingTrained panel of 18 general practitioners from four German states: Bavaria, Berlin, Rhineland Palatinate, and Saxony.Participants263 patients (66 men, 197 women) with moderate depression according to ICD-10 (international classification of diseases, 10th revision) codes F32.1 and F33.1.Interventions1050 mg hypericum extract (350 mg three times daily), 100 mg imipramine (50 mg, 25 mg, and 25 mg daily), or placebo three times daily.ResultsHypericum extract was more effective at reducing Hamilton depression scores than placebo and as effective as imipramine (mean −15.4 (SD 8.1), −12.1 (7.4), and –14.2 (7.3) respectively). Comparable results were found for Hamilton anxiety and clinical global impressions scales and were most pronounced for the Zung self rating depression scale. Quality of life was more improved in the standardised mental component scale of the SF-36 with both active treatments than with placebo but in the physical component scale was improved only by hypericum extract compared with placebo. The rate of adverse events with hypericum extract was in the range of the placebo group but lower than that of the imipramine group (0.5, 0.6, and 1.2 events per patient respectively).ConclusionsAt an average dose of 350 mg three times daily hypericum extract was more effective than placebo and at least as effective as 100 mg imipramine daily in the treatment of moderate depression. Treatment with hypericum extract is safe and improves quality of life.

Key messages

• Hypericum extract (STEI 300) was effective after 4, 6, and 8 weeks of treatment in patients with moderate depression
• Simultaneous analysis confirmed hypericum extract to be at least as efficacious as imipramine 100 mg daily after eight weeks of treatment
• Besides better antidepressive efficacy both hypericum extract and imipramine improved quality of life
• Patients tolerate hypericum extracts much better than they do tricyclics and therefore by improving patients'' compliance hypericum extracts are promising drugs for long term treatment

     

Antidepressant effects of light therapy and "natural" treatments for winter depression

Although bright light treatment may alleviate the symptoms of winter depression, it still remains to be clarified whether chronobiological mechanisms are involved in this antidepressant response. We studied the therapeutic action of bright light in 61 women with and 36 women without winter depression at the medical academic hospital near Novosibirsk (55 degrees North). Bright light was administered with cool-white incandescent lamp for seven days, two hours daily. The treatment started from either 8:00 (n = 29 patients and 16 controls) or 16:00 (n = 24 and 14, respectively) or 18:00 (n = 8 and 6, respectively). The subsets of bright light-treated subjects were then restudied in wintertime before and after one-week vacation in Firuza resort (south of Turkmeniya, 38 degrees North) (n = 19 and 0, respectively), in summertime (n = 42 and 18, respectively) and in the next winter before and after a week 30-min exposure in the morning hours to dim red light emitting “Light Cap” (n = 9 and 0, respectively). The results suggest that, in controls, mood slightly but statistically significantly improved after light treatment and in summer. In patients, the improvement of mood after one week of bright light was comparable with the effects of such “natural” treatments as trips south and transition from winter to summer seasons. Although next winter response to 0.5-h dim light was clinically significant, it was significantly worse compared to the previous response to 2-h bright light. Our therapeutic results indicate that, despite the different potential phase-shifting effect of bright light administered in the morning and in the second half of the day, the responses to all treatments are equally beneficial. This finding provides evidence against the view that circadian phase shifts are the key to the pathogenesis of winter depression and efficacy of light therapy. Although several different physiological effects of light therapy might be involved in the antidepressant response, none of them seems to be of more importance compared to psychological components of this response. Ours and earlier published reports on the independence of beneficial action of bright light from treatment timing support the suggestion that, in the open investigational trials, the placebo effect accounts for a large portion of the antidepressant response. We also reviewed several facts pointing to the close dependence of antidepressant effects of non-drug therapy upon patients' expectations and researchers' enthusiasm. In sum, unlike patients' chronobiology, their psychology seems to be most powerful mediator of the clinical response to bright light.     

Postpartum ovarian activity and uterine involution in non-seasonal Shiba goats,with or without nursing

Postpartum ovarian activity, uterine involution, and the relationship with hormonal profiles were studied in non-seasonal Shiba goats, with or without nursing of their kids. After parturition, does were allocated to one of two groups, with either weaning on the day of parturition (n = 3; non-nursing group) or weaning at 7–10 weeks after parturition (n = 4; nursing group). Blood sampling (starting 7 days prior to expected day of parturition) and transrectal ultrasound evaluations (starting 2 days after parturition) were conducted every other day or daily to monitor the follicular dynamics, uterus size, and the levels of plasma progesterone, blood glucose, and insulin concentration until at 3 weeks following the first postpartum ovulation. In the nursing group, blood samples were also collected every 10 min for an 8 h period on the day before weaning, 2 and 6 days after weaning, for the analysis of the pulsatile patterns of LH release. In all animals, the blood glucose concentrations increased transiently on the day before parturition and were significantly (p < 0.05) higher than those on the day of parturition (mean of 144 ± 48.8 mg/dl vs 63 ± 11.2 mg/dl). In the non-nursing group, the first postpartum ovulation was observed 9.3 ± 3.2 days after parturition, while in the nursing group, no ovulation occurred before weaning in any of the goats. Here ovulation was observed 18.8 ± 5.0 days after weaning, which was significantly (p < 0.05) later than in the non-nursing group. After first ovulation, all animals in both groups showed early luteal regression. No significant difference in the time required for the completion of uterine involution was recorded between the non-nursing and nursing groups (18.3 ± 4.2 days vs 19.3 ± 3.6 days, respectively), nor in the plasma LH pulse frequency obtained before (1.3 ± 0.5 pulses/8 h), 2 (1.3 ± 1.0 pulses/8 h) and 6 days (2.0 ± 0.8 pulses/8 h) after parturition, in the nursing group. It can be concluded that no ovulation occurs during nursing postpartum, suggesting that nursing is a determinant of the resumption of ovulation in these non-seasonal goats. Ultrasonic observations of the ovary suggest that uterine involution was not influenced by nursing or suckling.     

Bright light exposure augments cognitive behavioral therapy for panic and posttraumatic stress disorders: a pilot randomized control trial

Sleep and Biological Rhythms - Bright light (BL) therapy is clinically utilized for treatment of sleep–wake disorders through the manipulation of circadian oscillation. It is also extended to...     

Interaction between N-methyl-D-aspartate receptor antagonists and imipramine in shock-induced depression

In the past few years, literature has accumulated describing manifestation of seizures following administration of certain antidepressants. Such reports are of particular importance because depression is a frequent psychiatric problem associated with epilepsy. Therefore, in the view of the fact that NMDA receptor antagonists have been reported to reduce behavioural deficits and have been shown to be anticonvulsant, it was considered imperative to study their antidepressant effect using shock-induced depression model in mice. Presentation of inescapable foot shock significantly reduced ambulation and rearing in the open field arena and increased immobility duration in the FST. Pretreatment with imipramine, MK 801 and ketamine significantly prevented the effect of shock. Also, the combination of imipramine with either of the NMDA antagonists antagonised the effect of shock. Haloperidol, prazosin and ketanserin pretreatment modified the effect of these agents. These findings suggest an antidepressant effect of the NMDA receptor antagonists, and a complexity of neurotransmitter mechanisms, which are responsible for the occurrence of behavioural effects in shock-induced depression model.     

Radiopharmaceuticals targeting PSMA for imaging and/or therapy

Targeting the Prostate Specific Membrane Antigen (PSMA) is becoming increasingly more important for the management of prostate cancer patients at various stages. This review article describes selected radiolabelled PSMA inhibitors with optimized radiopharmaceutical properties for imaging and/or therapy.     

Computation by ensemble synchronization in recurrent networks with synaptic depression

While computation by ensemble synchronization is considered to be a robust and efficient way for information processing in the cortex (C. Von der Malsburg and W. Schneider (1986) Biol. Cybern. 54: 29–40; W. Singer (1994) Inter. Rev. Neuro. 37: 153–183; J.J. Hopfield (1995) Nature 376: 33–36; E. Vaadia et al. (1995) Nature 373: 515–518), the neuronal mechanisms that might be used to achieve it are yet to be uncovered. Here we analyze a neural network model in which the computations are performed by near coincident firing of neurons in response to external inputs. This near coincident firing is enabled by activity dependent depression of inter-neuron connections. We analyze the network behavior by using a mean-field approximation, which allows predicting the network response to various inputs. We demonstrate that the network is very sensitive to temporal aspects of the inputs. In particular, periodically applied inputs of increasing frequency result in different response profiles. Moreover, applying combinations of different stimuli lead to a complex response, which cannot be easily predicted from responses to individual components. These results demonstrate that networks with synaptic depression can perform complex computations on time-dependent inputs utilizing the ability to generate temporally synchronous firing of single neurons.     

Evaluation of 15 functional candidate genes for association with chronic otitis media with effusion and/or recurrent otitis media (COME/ROM)

DNA sequence variants in genes involved in the innate immune response and secondary response to infection may confer susceptibility to chronic otitis media with effusion and/or recurrent otitis media (COME/ROM). We evaluated single nucleotide polymorphisms (SNPs) in 15 functional candidate genes. A total of 99 SNPs were successfully genotyped on the Sequenom platform in 142 families (618 subjects) from the Minnesota COME/ROM Family Study. Data were analyzed for association with COME/ROM using the Generalized Disequilibrium Test (GDT). Sex and age at exam were adjusted as covariates, relatedness was accounted for, and genotype differences from all phenotypically discordant relative pairs were utilized to measure the evidence of association between COME/ROM and each SNP. SNP rs2735733 in the region of the mucin 5, subtypes A/C gene (MUC5AC) exhibited nominal evidence for association with COME/ROM (P = 0.002). Two additional SNPs from this region had P values<0.05. Other variants exhibiting associations with COME/ROM at P<0.05 included the SCN1B SNP rs8100085 (P = 0.013), SFTPD SNP rs1051246 (P = 0.039) and TLR4 SNP rs2770146 (P = 0.038). However, none of these associations replicated in an independent sample of COME/ROM families. The candidate gene variants examined do not appear to make a major contribution to COME/ROM susceptibility, despite a priori evidence from functional or animal model studies for a role in COME/ROM pathology.