High dose benzodiazepines prolong reaction times in chronic users who have major depressive and/or anxiety disorders.

AIM: Short term administration of benzodiazepines (BZD) was found to prolong reaction time (RT) in experimental studies. However, studies on long term BZD use did not always adjust for important confounders and showed inconsistent results. We aimed to identify a possible relationship between long term BZD use and RT in BZD users in this large cross-sectional, observational study. METHODS: The RTs of non-users (n = 2404) were compared with low (n = 288), intermediate (n = 74), and high dose BZD users (n = 57) in the Netherlands Study of Depression and Anxiety (NESDA). RTs were obtained from the Implicit Association Test. Analyses were adjusted for sociodemographic characteristics, health indicators, severity of psychopathology and antidepressant use. RESULTS: Of the NESDA participants, 419 subjects (14.8%) used BZDs. A higher dose of BZDs was associated with prolonged RTs (P = 0.01). When comparing the different dose groups, the high dose group, but not the low and medium dose groups, had significantly longer RTs than the non-users. CONCLUSIONS: Tolerance for the RT prolonging effect of relatively high doses of BZDs does not seem to develop. As prolonged RTs can have adverse consequences in daily life, BZDs should be prescribed conservatively at the lowest possible dose.

Determinants of initiated and continued benzodiazepine use in the Netherlands study of depression and anxiety.

BACKGROUND: Longitudinal research on determinants of initiated and continued benzodiazepine (BZD) use is inconsistent and has identified many possible determinants. It is unclear which of those are most important in the prediction of BZD use. We aimed to identify the most important predictors of initiated and continued BZD use. Therefore, we analyzed the most consistently identified determinants from previous research plus some new determinants. METHODS: We identified baseline and 2-year longitudinal predictors of initiated BZD use (vs nonuse) among 2205 baseline BZD nonusers and of continued use (vs discontinued use) among 369 baseline BZD users in the Netherlands Study of Depression and Anxiety using logistic regression analyses. RESULTS: During follow-up, BZD use was initiated by 4.9% of BZD nonusers at baseline. Initiated use was predicted by insomnia (odds ratio [OR], 1.60), enduring anxiety symptoms (OR, 2.02), entering secondary care during follow-up (OR, 2.85), and past BZD use (OR, 3.57). Positive life events during follow-up reduced the likelihood of BZD initiation (OR, 0.76). Of BZD users at baseline, 54.2% continued use during the entire follow-up period. Continuation of BZD use was predicted by higher age (OR, 1.03), severe anxiety (OR, 1.85), and a long duration of BZD use (OR, 1.54). Leaving secondary care was associated with less continued BZD use (OR, 0.29). CONCLUSION: Insomnia and anxiety were the main risk factors of initiated use, whereas advanced age and anxiety severity were the main risk factors of continued use. Sex, education, pain, and physical health seemed to be less important.

Correlates of (inappropriate) benzodiazepine use: the Netherlands Study of Depression and Anxiety (NESDA).

AIM: Results on determinants of benzodiazepine (BZD) use in general and inappropriate use were inconsistent and mostly univariate. The relative importance of sociodemographic, psychological and physical determinants has never been investigated in a comprehensive, multivariate model. METHODS: We included 429 BZD users and 2423 non-users from the Netherlands Study of Depression and Anxiety (NESDA) in order to investigate sociodemographic, psychological and physical determinants of BZD use and inappropriate use by logistic and linear regression analyses. RESULTS: BZDs were used by a considerable proportion of the 2852 NESDA participants (15.0%). BZD use was independently associated with older age, singleness, unemployment, treatment in secondary care, higher medical consumption (more severe) anxiety, depression (OR [95% CI]=1.95 [1.29, 2.93]), comorbidity, insomnia, SSRI (OR [95% CI]=2.05 [1.55, 2.70]), TCA and other antidepressant (OR [95% CI]=2.44 [1.64, 3.62]) use. Overall, BZD use was rarely in accordance with all guidelines, mainly because most users (82.5%) exceeded the recommended duration of safe use. Inappropriate use was independently associated with older age (ß=0.130) and chronic illnesses (ß=0.120). Higher scores on agreeableness were associated with less inappropriate use. CONCLUSIONS: Mentally or physically vulnerable subjects were most likely to use BZDs. The most vulnerable (i.e. the old and physically ill) BZD users were at highest risk of inappropriate BZD use. Without further evidence of the effectiveness of BZDs in long-term use, caution in initiating BZD prescriptions is recommended, particularly when patients are chronically ill and old, as those are most likely to display inappropriate use.

Long-term benzodiazepine use and salivary cortisol: the Netherlands Study of Depression and Anxiety (NESDA).

BACKGROUND: As benzodiazepines (BZDs) have anxiolytic effects, it is expected that they influence the stress system. During short-term treatment, BZD use was found to suppress cortisol levels. However, little research has been done on the effects of long-term BZD administration on the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: The association between long-term BZD use and cortisol levels was investigated in subjects of the Netherlands Study of Depression and Anxiety with a lifetime diagnosis of anxiety or depression (n = 1531). The subjects were categorized as "daily BZD users" (n = 96), "infrequent BZD users" (n = 172), and "nonusers" (n = 1263). Possible associations between characteristics of BZD use (dose, duration, and dependence) and salivary cortisol levels were analyzed. MAIN OUTCOME MEASURE: Subjects provided 7 saliva samples, from which 4 cortisol indicators were calculated: the cortisol awakening response, diurnal slope, evening cortisol, and cortisol suppression after ingestion of 0.5 mg of dexamethasone. RESULTS: Daily users used BZDs for a median duration of 26.5 months and had a median daily dosage of 6.0 mg as measured in diazepam equivalents. Evening cortisol levels were significantly lower in daily users (P = 0.004; effect size: d = 0.24) and infrequent users (P = 0.04; effect size: d = 0.12) compared to nonusers. We did not find significant differences in the cortisol awakening response, diurnal slope, or in the dexamethasone suppression test. CONCLUSIONS: Despite the finding of slightly lower evening cortisol levels in daily and infrequent BZD users compared to nonusers, results indicate that long-term BZD use is not convincingly associated with HPA axis alterations.

Relations of Dispositions toward Ridicule and Histrionic Self-Presentation with Quantitative and Qualitative Humor Creation Abilities.

Previous research has shown that humor and self-presentation are linked in several ways. With regard to individual differences, it turned out that gelotophilia (the joy of being laughed at) and katagelasticism (the joy of laughing at others) are substantially associated with the histrionic self-presentation style that is characterized by performing explicit As-If-behaviors (e.g., irony, parodying others) in everyday interactions. By contrast, gelotophobia (the fear of being laughed at) shows a negative correlation with histrionic self-presentation. In order to further contribute to the nomological network, we have explored whether the three dispositions toward ridicule and laughter as well as histrionic self-presentation are related to humor creation abilities. In doing so, we have assessed the four constructs in a study with 337 participants that also completed the Cartoon Punch line Production Test (CPPT, Köhler and Ruch, 1993, unpublished). In the CPPT, subjects were asked to generate as many funny punch lines as possible for six caption-removed cartoons. The created punch lines were then analyzed with regard to quantitative (e.g., number of punch lines) and qualitative (e.g., wittiness of the punch lines and overall wittiness of the person as evaluated by three independent raters) humor creation abilities. Results show that both gelotophilia and histrionic self-presentation were positively correlated with quantitative and qualitative humor creation abilities. By contrast, gelotophobia showed slightly negative and katagelasticism no associations with the assessed humor creation abilities. These findings especially apply to the subgroup of participants that created punch lines for each of the six cartoons and partly replicate and extend the results of a previous study by Ruch et al. (2009). Altogether, the results of our study show that individual differences in humor-related traits are associated with the quantity and quality of humorous punch lines. It is argued that behavior-related or performative humor creation tasks should be considered in addition to the CPPT in order to open up new avenues that can cross-fertilize research on individual differences in humor and self-presentation.

Correlates of benzodiazepine dependence in the Netherlands Study of Depression and Anxiety.

AIMS: Benzodiazepines (BZDs) are effective in the short term against anxiety and insomnia. However, some BZD users develop BZD dependence after a relatively short period of time. Therefore, we aimed to identify the risk factors of BZD dependence. DESIGN: An observational cohort study. SETTING: The Netherlands. PARTICIPANTS: Four hundred and one BZD users of the 2981 participants of the Netherlands Study of Depression and Anxiety (NESDA) were included. MEASUREMENTS: Socio-demographic, physical, psychological, addiction-related and BZD use-related characteristics were investigated as possible correlates of BZD dependence severity. Dependence severity was measured by the three subscales of the Benzodiazepine Self-Report Questionnaire, comprising problematic use, preoccupation and lack of compliance. FINDINGS: In multivariate analyses, problematic use was associated with more GP contacts in the past 6 months (ß = 0.170, P = 0.001) and severity of insomnia (ß = 0.145, P = 0.004). Preoccupation was related to anxiety severity (ß = 0.194, P = 0.001), antidepressant use (ß = 0.197, P < 0.001), alcohol dependence (ß = 0.185, P < 0.001) and a higher daily dosage of BZD (ß = 0.160, P = 0.001). Lack of compliance was associated with higher age (ß = 0.122, P = 0.03), unemployment (ß = 0.105, P = 0.04), insomnia (ß = 0.129, P = 0.01), antidepressant use (ß = 0.148, P = 0.002) and alcohol dependence (ß = 0.108, P = 0.02). CONCLUSIONS: Insomnia, antidepressant use and alcohol dependence may increase the risk of benzodiazepine dependence among individuals who use benzodiazepines.

Antidepressant use and salivary cortisol in depressive and anxiety disorders.

Antidepressants are an effective treatment for depressive and anxiety disorders. Those disorders are frequently accompanied by heightened cortisol levels. Antidepressants may affect hypothalamic-pituitary-adrenal axis functioning, the alteration of which could be partially responsible for treatment efficacy. The association between antidepressants and cortisol was investigated in 1526 subjects of the Netherlands Study of Depression and Anxiety who were grouped into 'serotonin reuptake inhibitor (SSRI) users' (n=309), 'tricyclic antidepressant (TCA) users' (n=49), 'other antidepressant users' (n=100), and 'non-users' (n=1068). All subjects had a current or past diagnosis of anxiety and/or depression. Subjects provided 7 saliva samples from which 3 cortisol indicators were calculated: cortisol awakening response (CAR), evening cortisol, and cortisol suppression after ingestion of 0.5mg dexamethasone. As compared to non-users, TCA users had a flattened CAR (effect size: Cohen's d=0.34); SSRI users had higher evening cortisol levels (d=0.04); and SSRI users showed decreased cortisol suppression after dexamethasone ingestion (d=0.03). These findings suggest that antidepressant subtypes are associated with distinct alterations of the HPA axis. TCA users, who showed a flattened CAR, displayed the strongest alterations of salivary cortisol.