Disruption of biological rhythms as a core problem and therapeutic target in mood disorders: the emerging concept of 'rhythm regulators'

Biological rhythms have always been considered to be disrupted in depression, with the predominant theory being that of hyperarousal. However, recent data suggest that it might be more appropriate to suggest that depressed patients are incapable of achieving and maintaining the particular level of internal homeostasis which permits them to function smoothly, to lower the level of arousal during sleep sufficiently so that quality of sleep is good, and to increase this level enough during the day so the person can function properly. Therefore, the transition from one state to another is somewhat problematic, delayed, incomplete and desynchronised. Thus, agents with a 'rhythm stabilising' effect could be beneficial in the treatment of mood disorders. Such an agent should have a beneficial effect on restoring and stabilising the rhythm of a physiological function while not pushing it towards a specific pole, or inducing the opposite pole; it should also allow response to internal and environmental stimuli and zeitgebers, and restore synchronisation of the various body rhythms while not inducing or worsening desynchronisation. Agomelatine could represent the first of a new class of 'rhythm stabilising antidepressants', but further research is necessary to support this theory

Pharmaceutical treatment of acute bipolar depression

The treatment of bipolar depression is one of the most challenging fields in contemporary psychiatry. The best data concern the antipsychotics quetiapine and the olanzapine-fluoxetine combination. However, the usefulness of antidepressants in bipolar depression remains controversial; positive data are available for fluoxetine but negative results have been published for paroxetine. Accumulated knowledge so far suggests that bipolar patients need continuous administration of an antimanic agent even during the acute depressive phase. Although our knowledge is indeed limited, the development of guidelines for polypharmacy is necessary and should be done as soon as possible

Antidepressant drugs and the response in the placebo group: the real problem lies in our understanding of the issue

In a recent paper, Horder and colleagues (Horder et al., 2010, J Psychopharmacol 25: 1277–1288) have suggested that the mainproblem in the Kirsch analysis is methodological. We argue that the results are similar irrespective of the method used. In our opinion the data suggest that placebo and drug effects are non-additive: antidepressants act independently of depression severity, while the placebo effect is present only in milder cases. While the response in the placebo group is due to unstable ‘noise’ and ‘artefacts’, the medication effect is reliable, valid and stable

Report of three cases that received maintenance treatment with risperidone as a mood stabilizer

INTRODUCTION: The current study is a short report of 3 cases of bipolar patients. MATERIAL AND METHODS: Three bipolar patients were prospectively followed up. All were partial responders to lithium therapy alone, and unresponsive to other therapies (anticonvulsants, antidepressants, typical antipsychotics, various combinations). RESULTS: All manifested complete remission of symptoms after combination therapy with lithium (plasma levels above 0.8 mEq/lt) plus 1–3 mg of risperidone daily. The two of them are still free of symptomatology during the maintenance period for 28 and 38 months respectively. The third patient, after several months during which she was free of symptomatology discontinued lithium against the psychiatrist's advise and received only 3 mg of risperidone daily. For the next 15 months the patient was under risperidone monotherapy and free of symptomatology. She discontinued therapy to become pregnant, the illness recurred several times during pregnancy and after the delivery the patient restarted risperidone therapy. She was free of symptoms for the following 9 months until her last follow-up. DISCUSSION: The current study provides preliminary evidence concerning the long term efficacy of risperidone in the treatment of bipolar patient

Is there a dysfunction in the visual system of depressed patients?

BACKGROUND: The aim of the current study was to identify a possible locus of dysfunction in the visual system of depressed patients. MATERIALS AND METHODS: Fifty Major Depressive patients aged 21–60 years and 15 age-matched controls took part in the study The diagnosis was obtained with the SCAN v 2.0. The psychometric assessment included the HDRS, the HAS, the Newcastle Scales, the Diagnostic Melancholia Scale and the GAF scale. Flash Electroretinogram and Electrooculogram were performed in all subjects. The statistical analysis included ANCOVA, Student's t-test and Pearson Product Moment Correlation Coefficient were used. RESULTS: The Electro-oculographic findings suggested that all subtypes of depressed patients had lower dark trough and light peak values in comparison to controls (p < 0.001), while Arden ratios were within normal range. Electroretinographic recordings did not reveal any differences between patients and controls or between subtypes of depression. DISCUSSION: The findings of the current study provide empirical data in order to assist in the understanding of the international literature and to explain the mechanism of action of therapies like sleep deprivation and light therapy

Off-label indications for atypical antipsychotics: A systematic review

INTRODUCTION: With the introduction of newer atypical antipsychotic agents, a question emerged, concerning their use as complementary pharmacotherapy or even as monotherapy in mental disorders other than psychosis. MATERIAL AND METHOD: MEDLINE was searched with the combination of each one of the key words: risperidone, olanzapine and quetiapine with key words that refered to every DSM-IV diagnosis other than schizophrenia and other psychotic disorders, bipolar disorder and dementia and memory disorders. All papers were scored on the basis of the JADAD index. RESULTS: The search returned 483 papers. The selection process restricted the sample to 59 papers concerning Risperidone, 37 concerning Olanzapine and 4 concerning Quetiapine (100 in total). Ten papers (7 concerning Risperidone and 3 concerning Olanzapine) had JADAD index above 2. Data suggest that further research would be of value concerning the use of risperidone in the treatment of refractory OCD, Pervasive Developmental disorder, stuttering and Tourette's syndrome, and the use of olanzapine for the treatment of refractory depression and borderline personality disorder. DISCUSSION: Data on the off-label usefulness of newer atypical antipsychotics are limited, but positive cues suggest that further research may provide with sufficient hard data to warrant the use of these agents in a broad spectrum of psychiatric disorders, either as monotherapy, or as an augmentation strategy