Subthreshold mood symptoms in patients with fibromyalgia and rheumatoid arthritis.

OBJECTIVES: Although several findings have highlighted the prevalence of Axis I psychiatric disorders in fibromyalgia (FM) and rheumatoid arthritis (RA), very little information is available on the prevalence of subthreshold mood symptoms in these conditions. Therefore, we aimed at comparing the prevalence of subthreshold mood symptoms in rheumatic patients suffering from FM and RA. The hypothesis is that subthreshold mood symptoms are more represented in FM, given the evidence of higher rates of Axis I psychopathology in FM than in RA. METHODS: Sixty patients suffering from FM and 50 from RA, assessed according to the American College of Rheumatology (ACR) criteria, selected in a Rheumatology Department, were included in the study. The subthreshold affective symptoms were assessed by means of the Mood Spectrum-Self Report (MOODS-SR). RESULTS: The results showed that FM patients presented significantly higher scores than RA patients in 'mood depressive', 'cognition depressive' domains and in total depressive component. CONCLUSIONS: The present study demonstrates that subthreshold depressive symptoms are more represented in FM than in RA patients. This fact could play a role in the worse quality of life and in the major perception of pain which characterises FM.

Lifetime post-traumatic stress symptoms are related to the health-related quality of life and severity of pain/fatigue in patients with fibromyalgia.

OBJECTIVES: The aim of the present study was to investigate the impact of lifetime potentially traumatic events, including losses, and of post-traumatic stress symptoms on the severity of illness and health-related quality of life in patients with fibromyalgia (FM). METHODS: Seventy patients with FM, diagnosed according to the American College of Rheumatology criteria, were consecutively enrolled at the Unit of Rheumatology of the University of Pisa, Italy. Assessments included: SCID-I/P; the Fibromyalgia Impact Questionnaire (FIQ) and the Medical Outcomes Study Short Form-36 Health Survey (MOS SF-36), for the severity of pain; the Health-Related Quality of Life (HRQoL); the Trauma and Loss Spectrum Self-Report (TALS-SR) life-time version. RESULTS: The FIQ total score was related to the number of loss events (Domain I) and to symptoms of grief reactions (Domain II) and re-experiencing (Domain V) of the TALS-SR. The 'VAS fatigue' scores (FIQ) were significantly related to the TALS-SR symptoms of grief reactions (Domain II) and re-experiencing (Domain V). The Mental Component Summary and Bodily Pain scores of the MOS SF-36 were significantly related to all TALS-SR domains, the latter with the exception of the VIII (Arousal). CONCLUSIONS: Our results corroborate the presence of a relationship between the lifetime exposure to potentially traumatic events, in particular loss events, and lifetime post-traumatic stress symptoms and the severity of illness and HRQoL in patients with FM.

Spasmophilia comorbidity in fibromyalgia syndrome.

OBJECTIVES: To evaluate the role of spasmophilia (SP) in fibromyalgia syndrome (FM). METHODS: Three hundred and fourteen patients (280 F, 34 M) with a diagnosis of FM or FM and spasmophilia (FM+SP) were recruited. Clinical assessment of patients and controls included the Questionnaires FIQ, HAQ and the tender point (TP) count. Life-time or ongoing psychiatric aspects were evaluated by trained psychiatrists by means of the classic scales: Structured Clinical Interview (SCID) for DSM-IV. The following analysis were evaluated: cytokine (IL1, IL2, IL6, IL8, IL10), TNF-α, cortisol, GH, ACTH, IGF1, 5HT, intracellular Mg, plasma calcium p(Ca), PTH, (25(OH)D) and thyroid functionality. Some typical symptoms were investigated. RESULTS: Eighty-one patients resulted positive for spamophilia (FM+SP), while 233 resulted negative for spasmophilia (FM). The mean TP number resulted higher in the FM group (15.33±3.88) with respect to FM+SP (12.88±6.17, p=0.016), while FIQ and HAQ did not differ between the two studied groups. FM patients exhibited a higher frequency of psychiatric disorders with respect to FM+SP patients (72% FM vs. 49% FM+SP, p<0.01). In particular the frequency of depression was 65.5% FM vs. 35% FM+SP (p<0.01). CONCLUSIONS: The presence of spasmophilia seems to influence psychiatric comorbidity which was less prevalent in FM+SP patients. FM is indeed characterised by an abnormal sensory processing of pain that seems to result from a combination of interactions between neurotransmitters, stress, hormones and the nervous system; spasmophilia would seem to be more linked to a dysfunction at the neuromuscular level.

Manic spectrum symptoms are correlated to the severity of pain and the health-related quality of life in patients with fibromyalgia.

OBJECTIVES: We aimed at investigating the impact of lifetime manic spectrum symptoms on the severity of pain and the health-related quality of life (HRQoL) in patients with fibromyalgia (FM). METHODS: One hundred and sixty-seven patients with FM, assessed according to the ACR criteria, were consecutively enrolled. Psychiatric diagnoses were carried out following the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV-TR). The severity of pain and the HRQoL of FM patients was measured by means of the Fibromyalgia Impact Questionnaire (FIQ) and the Medical Outcomes Study Short Form-36 Health Survey (MOS SF-36); the mood spectrum symptomatology by means of the Mood Spectrum-Self Report (MOODS-SR). RESULTS: A high rate of lifetime manic symptoms was detected and resulted as related to the Pain Visual Analogic Scale ("pain VAS") of the FIQ and the FIQ total scores as well as to the "bodily pain", and to the physical and mental component summary scores of the MOS SF-36, both in the whole sample (n=167) and in FM patients without bipolar disorder (n=160). CONCLUSION: Our results highlight the need to pay more attention to manic spectrum symptoms and features in FM patients, because of their relationship with the severity of pain and with a worse HRQoL.

Cytokine patterns in fibromyalgia and their correlation with clinical manifestations.

OBJECTIVE: To examine the possible role of the soluble factor in fibromyalgia (FM) by studying the correlation of cytokine levels with the patients' clinical and psychiatric profile. METHODS: Eighty FM patients underwent clinical and psychiatric evaluations, and plasma levels of cytokines (IL-1, IL-6, IL-8, IL-10, TNF-alpha), aspecific markers of inflammation, rheumatoid factor (RF), anti-extractable nuclear antigen (ENA) antibodies, and anti-nuclear factor (FAN) were measured. RESULTS: Higher levels of IL-10, IL-8 and TNF-alpha were found in FM patients than in controls. Significant correlations between the biochemical parameters and clinical data were found. CONCLUSION: The higher levels of cytokines found in FM patients suggest the presence of an inflammatory response system (IRS) and highlight a parallel between the clinical symptoms and biochemical data. They support the hypothesis that cytokines may play a role in the clinical features of fibromyalgia. In addition, the similar cytokine patterns found in FM patients with different psychiatric profiles suggests that IRS impairment may play a specific role in the disease.

Clozapine for treatment-refractory schizophrenia, schizoaffective disorder, and psychotic bipolar disorder: a 24-month naturalistic study.

BACKGROUND: The aim of this study was to evaluate the 24-month response to clozapine in patients with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder. METHOD: Ninety-one psychotic patients with a principal DSM-III-R diagnosis of schizophrenia (N = 31), schizoaffective disorder (N = 26), or bipolar disorder with psychotic features (N = 34) were treated naturalistically with clozapine at flexible dosages over a 24-month period. Improvement was assessed by the 18-item Brief Psychiatric Rating Scale and the Clinical Global Impressions-Severity of Illness scale. RESULTS: All patients showed significant improvement 24 months from intake (p < .001). Such an improvement was significantly greater among patients with schizoaffective disorder or bipolar disorder than in patients with schizophrenia (p < .05). The presence of suicidal ideation at intake predicted greater improvement at endpoint. CONCLUSION: Clozapine appears to be effective and relatively well tolerated in acute and long-term treatment of patients with psychotic bipolar disorder or schizoaffective disorder who have not responded to conventional pharmacotherapies.

Electroconvulsive therapy in medication-nonresponsive patients with mixed mania and bipolar depression.

BACKGROUND: The aim of this study was to investigate the effectiveness of electroconvulsive therapy (ECT) in medication-nonresponsive patients with mixed mania and bipolar depression. METHOD: Forty-one patients with mixed mania (DSM-IV diagnosis of bipolar I disorder, most recent episode mixed) and 23 patients with bipolar depression (DSM-IV diagnosis of bipolar I disorder, most recent episode depressed) consecutively assigned to ECT treatment were included in this study. Subjects were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impressions-Severity of Illness scale (CGI-S). Assessments were carried out the day before starting ECT, 48 hours after completion of the third session (T1), and a week after the last session of ECT (T2). RESULTS: Both groups received an equal number of ECT sessions (mean +/- SD = 7.2 +/- 1.7 vs. 7.3 +/- 1.6). In both groups, within-group comparisons showed that there was a significant reduction in CGI-S score (mixed mania, p <.0001 at T1 and T2; bipolar depression, p < .01 at T1, p < .0001 at T2), MADRS total score (both groups, p < .0001 at T1 and T2), BPRS total score (mixed mania, p < .0001 at T1 and T2; bipolar depression, p < .001 at T1, p < .0001 at T2), and BPRS activation factor score (mixed mania, p < .0001 at T1 and T2; bipolar depression, NS at T1, p < .01 at T2). Between-group comparisons revealed that patients with mixed mania showed significantly greater decrease in MADRS score (p < .001) and a greater proportion of responders (CGI-S) than patients with bipolar depression at endpoint (56% [N = 23] vs. 26% [N = 6], p = .02). Patients with mixed mania showed a greater reduction in suicidality, as measured by MADRS score, than patients with bipolar depression (p < .02). CONCLUSION: In our study, ECT was associated with a substantial reduction in symptomatology, in both patients with mixed mania and those with bipolar depression. However, the mixed mania group exhibited a more rapid and marked response as well as a greater reduction in suicidal ideation. Response to ECT was not influenced by the presence of delusions.

Simultaneous analysis of clozapine, clomipramine and their metabolites by reversed-phase liquid chromatography.

1. The authors present here a sensitive and rapid reversed-phase liquid chromatographic method which enables the simultaneous analysis in plasma of two different drugs and their metabolites: the atypical neuroleptic clozapine and the tricyclic antidepressant clomipramine. 2. Samples and the internal standard (dibenzepine) were extracted through automated solid-phase procedure, evaporated dryness and injected into the chromatograph. Mobile phase was a mixture of water and acetonitrile (63:37, v:v) containing TEMED and triethylamine. The total chromatographic time was of 14 min and analyte peaks were detected by means of an ultraviolet spectrophotometer preset at 254 nm. 3. Results revealed an assay sensitivity of 5 microg/L for clozapine or norclozapine and of 10 microg/L for clomipramine and desmethylclomipramine. Recoveries for these drugs and their metabolites were more than 60% and their coefficient of variation (within day and day-to-day) ranged from 1.3 % to 2.5 %. In spiked plasma, within day and day-to-day coefficients of variability (CV) were less than 5%. The simultaneous evaluation of these two drugs with adequate sensitivity and precision makes it particularly useful for therapeutic drug monitoring during mono- or polypharmacotherapy.

Citalopram in refractory obsessive-compulsive disorder: an open study.

This study aimed to evaluate the effect of citalopram in patients with refractory obsessive-compulsive disorder (OCD) which had not responded to previous antiobsessional treatments. Eighteen patients were selected for this study: they had been suffering from OCD, according to DSM-IV criteria, for at least 2 years and had various comorbid disorders. All had been treated with serotonin reuptake inhibitors at adequate dosages for at least 6 months, but had failed to respond. Consequently, they were shifted to citalopram, titrated up to the dose of 40 mg, within 2 weeks. After 4 months of this regimen, 14 out of the total of 18 patients had shown a reduction in OC symptoms, as assessed by the decrease in the Yale-Brown Obsessive Compulsive Scale total score; no relevant side-effects were reported, except for a mild nausea in four patients within the first few days of treatment, which quickly disappeared. The use of citalopram would appear to be an useful strategy in refractory OCD cases.

Clozapine as a treatment tool: only in resistant schizophrenic patients?

Evidence indicates that clozapine is effective in the management of treatment-resistant schizophrenia and in affective psychoses. To examine whether affective components within the boundaries of the schizophrenia spectrum imply specific psychopathological characteristics of response to treatment, 60 patients with a treatment-resistant schizophrenia spectrum disorder who were treated with clozapine (75-600 mg/d) were evaluated in a naturalistic, open, follow-up study. The group comprised 41 patients with and 19 without bipolar features (43 men and 17 women, mean age 34.3 years). Patients were evaluated with the Brief Psychiatric Rating Scale (BPRS) during the first year of treatment. The results show a significant improvement in scores in both groups (P < 0.001) compared with the baseline evaluation. A higher percentage of responders was seen in the 'affective' group. No typical psychopathological characteristic or symptom cluster predicting the response to treatment was identified. During the study, 15 patients discontinued treatment: six for lack of efficacy, five for non-compliance and four for adverse events. The study confirms the efficacy of clozapine in the treatment of schizophrenia spectrum disorders, particularly in patients with bipolar features.

Patterns of caffeine consumption in psychiatric patients. An Italian study.

PURPOSE: The aim of the present study was to explore and compare the caffeine intake, intoxication, withdrawal and dependence prevalence in Italian psychiatric patients and healthy subjects. MATERIALS AND METHODS: Three hundred and sixty-nine out- and inpatients, suffering from different psychiatric disorders, and 104 healthy subjects were included in the study. They were assessed by the SCID and by a structured interview for caffeine intoxication and withdrawal and for substance dependence applied to caffeine use. RESULTS: Patients and healthy subjects did not differ in terms of current caffeine intake (mg/day, mean+/-SD: 281+/-325 vs. 288+/-148, respectively), while the maximum lifetime intake of caffeine was significantly higher in the first group (mg/day, mean SD: 630+/-549 vs. 504+/-344, respectively; F=4.897, p=.03) where it was significantly related to the CGI severity item scores (rho=.107; p=.04). In both patients and healthy subjects, a lower age was related to a higher current caffeine intake, while both current and maximum lifetime caffeine intake in the healthy subjects were significantly higher in men than in women. The patients suffering from eating disorders reported higher current caffeine intake than those with anxiety or mood disorders. The prevalence of dependence and intoxication was significantly higher in the patients than in the healthy subjects, without inter-group differences. Healthy subjects showed a trend towards a higher prevalence of withdrawal. CONCLUSIONS: Our study highlights the need that a more accurate attention should be paid to the caffeine use which seems to be strongly, although generically, related to different psychiatric disorders.

[Treatment of insomnia related to depressive disorders. Effects of zolpidem versus flunitrazepam administration and withdrawal evaluated in a double-blind study]. / Terapia dell'insonnia correlata con i disturbi depressivi. Studio in doppio cieco sugli effetti della somministrazione e della sospensione di zolpidem versus flunitrazepam in pazienti depressi insonni.

The effects of a 15 day treatment with zolpidem (10 mg) and with flunitrazepam (1 mg) on Insomnia Disorders Related to Depressive Disorders (DSM-III-R) have been evaluated on 30 depressive in-patients (mean age 42.3 +/- 9.8). The trial has been carried out on double blind condition after 5 days of single blind placebo administration. Withdrawal effects have been evaluated in single blind condition on a 10 day period after drugs discontinuation. Patient's diagnosis was Major Depression or Dysthymia according to DSM-III-R; inclusion criteria were insomnia (total sleep time < or = 6 h, sleep latency > or = 30 min, wake after sleep onset > or = 30 min, No of awakenings > or = 3) refractory to clomipramine administration at constant dose (75-150 mg/day among patients). Both drugs have been followed by a rapid, significant diminution of insomnia as demonstrated by significant changes at Stanford Sleepiness Scale and Saint Mary Hospital Sleep Questionnaire and by a significant reduction of HDRS total scores. No clinical phenomena of rebound insomnia were detected after zolpidem and flunitrazepam withdrawal. Drug discontinuation however was followed by the slow increase of the score on insomnia items, approximating basal values at the end of the 10 day period after zolpidem and flunitrazepam withdrawal. A parallel increase of HDRS total score was also detected; HDRS changes were mainly due to the increase of the items anxiety somatic, general somatic symptoms, gastrointestinal somatic symptoms, hypochondriasis. The study confirms the therapeutic efficacy of zolpidem and of flunitrazepam in the treatment of insomnia resistant to antidepressant drugs in depressed patients. They also suggest that early drug discontinuation is frequently associated with clinical relapse of insomnia and of several other symptoms correlated with the affective pathology.

Affective temperament in the eating disorders.

BACKGROUND: In this study, we investigate the affective temperamental characteristics in a sample of ED (eating disorder) patients. METHODS: 49 ED patients diagnosed by the SCID (Structured Clinical Interview for DSM-IV), were divided into two groups on the basis of the presence or absence of Binge Eating (restricting-anorexia nervosa [R-AN]= 16; Binge Eaters= 33). All patients were administered the TEMPS-I (Temperament Evaluation Memphis Pisa Semistructured - Interview), to assess affective temperament. A third group of controls (N= 1010), derived from a study with the TEMPS-I on normal subjects, was included for comparison. RESULTS: A full affective temperament was not found in patients of the restricting group. By contrast 24% of the binge eating group had a full affective temperament of one of three types. Comparing the three temperaments for the three groups, only cyclothymic temperament proved to be significant, with higher levels in the binge eating group (p<0.01). CONCLUSIONS: In this study, people with R-AN do not show a full affective temperament. However, people with binge eating, had depressive and hyperthymic temperament, and displayed higher level of cyclothymic temperament than the normal population. The findings of this study add to a growing literature on temperament in people with ED; particularly, they add to the view that may be various paths leading to R-AN, and these may differ from those of binge eating.

[Abrupt shift to zolpidem, a new imidazopyridine hypnotic, in insomniac patients previously treated with benzodiazepine hypnotics]. / Passaggio ex-abrupto a zolpidem, nuovo ipnotico imidazopiridinico, in pazienti insonni già in trattamento con ipnotici benzodiazepinici.

Zolpidem is a new imidazopyridine hypnotic with a pharmacological profile substantially different from benzodiazepines. In this observational multicenter study the possibility of shifting to zolpidem (10 mg at N1, 15 or 20 after N1) insomniac patients previously taking (for at least 15 days and not longer than 3 months) standard posology of triazolam (0.125-0.25 mg), lorazepam (1 mg) or lormetazepam (1 mg) was assessed. For ethical reasons the patients were mandatorily to be insomniacs despite their taking hypnotics or not tolerating them. Patients enrolled were 299 of whom 276 evaluable (139 males and 136 females; mean age 48.67 +/- 14.64, range 18-83). Study duration was 7 nights with visits at N0 (baseline), N1 (after 1st night), N3 (after 3rd night) and N7 (final evaluation); on each visit the Saint Mary Hospital Sleep Questionnaire and the benzodiazepine withdrawal symptom's rating scale were administered; moreover, after N7, investigators were asked a judgement of feasibility of such a shift. In 229 (83.5%) out of 274 patients such a shift to zolpidem was considered successfully (no occurrence of symptoms and/or signs of previously taken hypnotic withdrawal); in the remaining 45 patients, just 17 (6.2%) seemed to be real unsuccessful cases (reactions mild and transient, anyhow). In conclusion abrupt shift to zolpidem appeared to be largely feasible in the patients studied.