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Further evidence on the interplay between benzodiazepine and Z-drug abuse and emotion dysregulation
Abstract
Background: Long-term benzodiazepine (BDZ)/Z-drug use, which is a risk factor for dependence, is frequent in neuropsychiatric conditions, especially emotional disorders. Also, BDZ/Z-drug misuse is associated with increased emotion dysregulation symptoms. This study aimed to investigate neuropsychiatric distress in patients with BZD/Z-drug use disorder, with particular attention to emotional symptoms.
Methods: Forty-two patients hospitalized for BZD/Z-drug use disorder (males/females= 20/22) were enrolled and dichotomized into a high-dose and a low-dose BZD/Z-drug user group. Neuropsychiatric distress was measured using standardized measures. The relationship between symptom profiles and BZD/Z-drug use disorder severity was explored using t-tests and negative binomial regression analyses.
Results: Twenty-seven patients (61.9%) presented with one or more psychiatric disorders, mostly an emotional disorder. Ten patients had a lifetime history of suicide attempt(s) (23.8%), while 11 presented recent suicidal ideation (26.2%), which resulted in suicidal behavior in 2 cases. High rates of depression, anxiety, and emotion dysregulation were reported. The high-dose BZD/Z-drug user group presented with higher depressive symptoms (p = 0.016) and emotion dysregulation (p = 0.044) than the low-dose BZD/Z-drug user group. Further, the higher the depressive symptomatology, the more severe was the BZD/Z-drug abuse (p = 0.028).
Limitations: Long-term patterns of BDZ/Z-drug use disorder among patients with emotional disorders and the role of other potential risk factors, such as gender, other substance use disorder, and personality disorders, need further investigation in larger samples.
Conclusions: This study showed high emotional symptoms among patients with BZD/Z-drug use disorder, with severe depression being associated with a more severe BZD/Z-drug dependence.
... In response to calls for more accessible and integrated support for BDZ cessation (Colizzi, Meneghin, Bertoldi, & Lugoboni, 2021;Coteur et al., 2020), digital mental health technologies may provide an answer. To date, only one study (Parr, Kavanagh, Young, & Mitchell, 2011) has utilised some digital components when evaluating a BDZ reduction and dependence intervention program that involved cognitive behaviour therapy (CBT). ...
... Improvements in quality of life and emotional dysregulation are also extremely positive, as emotional dysregulation has recently been found to be elevated in BDZ drug use disorder (Colizzi et al., 2021). Colizzi et al. therefore advocated for the greater use of integrated interventions (e.g., cognitive-behavioural and pharmacological) to better manage the emotional difficulties that people with BDZ use disorder commonly experience. ...
Introduction
Benzodiazepines (BDZs) are often inappropriately prescribed to manage anxiety and insomnia for longer-term use, despite guidelines recommending short-term use (i.e., <4 weeks). A range of harms can occur rapidly with regular use, and dependence can make stopping BDZs challenging. Evidence shows that a combination of BDZ tapering and psychological support are effective interventions, yet are not widely accessible.
Methods
This was a one-group pilot trial of a 6-week fully automated self-help BDZ digital intervention (‘BDZ digital health’), providing guidance on how to safely taper BDZs as well as psychological support. The trial was undertaken with Australian adults considering a reduction and/or withdrawal from their BDZ (N = 43). Participants were assessed at pre-intervention (Week 0), during intervention (Week 3), post-intervention (Week 6), and at a 3- and 6-month follow-up (Week 18 and 30 respectively).
Results
Reductions in BDZ use and self-reported dependency were observed over the course of the intervention. Significant symptom reductions in anxiety, insomnia, depression, psychological distress, and emotional dysregulation, as well as improvements in mental wellbeing and quality of life were observed when looking across all timepoints. However, the specific assessment timepoint changes for depression and psychological distress did not reach significance from the pre- to post-intervention timepoint. The intervention acceptability ratings were in the moderately high to high range.
Discussion
The preliminary results of the pilot trial suggest that BDZ digital health is an acceptable and promising self-help digital intervention to assist adults reducing and withdrawing from their BDZs, and to improve their mental health and wellbeing.
Trial registration: ACTRN12617000574347 (24/04/2017).
... Moreover, data published by the Italian Medicines Agency (AIFA) also highlighted the finding that the use of benzodiazepines in Italy slightly decreased (−1.6%) between 2021 and 2022, likely due to efforts to promote safer prescribing practices. Nevertheless, an estimated range from 6% to 76% of benzodiazepine users become long-term users during the years of treatment, with 15% to 30% of users developing moderate to severe withdrawal and/or rebound symptoms [18]. ...
The use of benzodiazepines is strongly associated with an increased risk of traffic accidents due to their side effects of sedation and drowsiness, which can significantly impair driving performance. The main aim of our study was to investigate the trend of benzodiazepine use over nine years (2015–2023) in a population of 15,988 subjects who had their license suspended for driving under the influence (DUI) of alcohol or drugs. Among the 15,988 users accessed to our laboratory, 924 tested positive for at least one benzodiazepine. An increase in the number of positive-testing users was observed in the period 2015–2018, followed by a slight decrease in 2019. Overall, the trend of benzodiazepine use was stable over the next four years (2020–2023), with the highest incidence in 2022. The most common benzodiazepines, and/or metabolites, found in urine samples were α-OH-alprazolam (28.66%; n = 366) and oxazepam (27.25%; n = 348). Several cases of mixed positivity were observed in the study population. The main substances taken with benzodiazepines were cocaine and Δ9-tetrahydrocannabinol. Our findings suggest that people taking benzodiazepines should be monitored, as these have a relevant impact on driving ability in addition to significant interindividual differences in the behavioral effects of benzodiazepines on driving performance.
... Despite their pharmacological benefits, benzodiazepines have a higher risk to induce dependency, withdrawal symptoms [1,5,21], gait disturbances and respiratory failures [19]. Treatments with benzodiazepines can cause sleep and mood disorders, as well as cognitive impairments and suicidal behaviours [22,23]. Developing new and safer agents for the treatment of alcohol withdrawal-anxiety, targeting the GABAergic neurotransmission is needed. ...
Ethanol withdrawal syndrome is a life-threatening state that results from a sudden termination of chronic alcohol intake. One of the manifestations of ethanol withdrawal syndrome is anxiety. Dichrocephala integrifolia is a plant used in Africa in the treatment of alcohol use disorders. This study aimed to evaluate the effects of Dichrocephala integrifolia on ethanol withdrawal anxiety in mice. Young adult Swiss mice were arranged into seven groups of six mice each. Groups II to VII received ethanol in increasing concentration for 20 days. Following ethanol withdrawal, mice were administered distilled water (Group II), Dichrocephala integrifolia (25,50,100 and 200 mg/ kg) (Groups III-VI) or diazepam (Group VII). Behavioural assessments were performed using the elevated plus maze, the open field and the hole board tests. Gamma-aminobutyric acid (GABA) concentration, GABA-Transaminase and glutamic acid decarboxylase activities were assessed in the brain. In the elevated plus maze, Dichrocephala integrifolia (100 mg/kg) significantly (p < 0.01) increased the percentage of open arms entries from 20.5 ± 1.56% in the negative control, to 65.3 ± 2.46%. In the hole board, the number of head dipping raised from 27.17 ± 0.60 in the negative control to 61.33 ± 2.82 (p < 0 0.01) at the dose 200 mg/kg of Dichrocephala integrifolia. Likewise, diazepam, Dichrocephala integrifolia (200 mg/kg) significantly (p < 0.01) raised GABA concentration from 267.70 ± 5.18 µg/g of tissue in the negative control to 395 ± 5.55 µg/g of tissue. The plant extract (200 mg/kg) reduced the activity of GABA-Transaminase from 101 ± 2.60 pg/min/mg of tissue in the negative control to 42.5 ± 2.35 pg/min/mg of tissue. From these results, we can conclude that, by enhancing the GABAergic neurotransmission, Dichrocephala integrifolia has anxiolytic activities against ethanol withdrawal anxiety and can therefore be a good drug candidate for the treatment of alcohol addiction.
... Our findings are consistent with other community studies reporting greater cannabis and sedative use among individuals exposed to traumatic experiences (Guina et al., 2016;Kevorkian et al., 2015;Pakdaman et al., 2021) and a mediating effect of dissociation and emotion dysregulation on the relationship between traumatic experiences and substance use (Klanecky et al., 2012;Schimmenti et al., 2022;Wolff et al., 2016). In light of the "self-medication hypothesis" (Khantzian, 1997), it is thus possible to hypothesize that sedatives, cannabis, and tobacco use might represent for some individuals a way to cope with depressive, sleep, and posttraumatic stress symptoms, arising from traumatic experiences (Colizzi et al., 2021;Murphy et al., 2018;Musetti et al., 2016;Sideli et al., 2019). In this context, substance addictive behaviors might be conceived as a form of "chemical dissociation," through which individuals compartmentalize distressing emotions and thoughts and detach themselves from their body and the reality (Somer et al., 2010), when other endogenous avoidant strategies were not effective. ...
Accumulating evidence suggests that substance addictive behaviors are associated with traumatic experiences, emotion dysregulation, and psychopathological symptoms. Emotion dysregulation may contribute to initiating and sustaining addictive behaviors, as a way to cope with interpersonal trauma. However, the interplay between interpersonal trauma, emotion dysregulation, and substance addictive behaviors is still understudied. An online survey was disseminated via snowball sampling. One thousand four hundred and forty-six individuals from the Italian general population were assessed for substance addictive behaviors, interpersonal trauma, emotion dysregulation, and psychopathological symptoms. A correlation network approach was used to examine the associations among these variables. Positive relationships were found between interpersonal trauma, emotion dysregulation, and substance addictive behaviors. Emotional neglect bridged the other types of trauma with substance use and psychopathology. Among psychopathological variables, depression, anxiety, and impaired personality functioning symptoms had the highest strength. Emotion dysregulation had the highest bridging. The findings suggest that psychopathological symptoms, emotion dysregulation, and emotionally traumatic experiences play a significant role in the activation of the addictive behavior network. Promoting emotion regulation strategies might be part of preventative actions and early intervention programs for substance addictive behaviors.
Purpose of Review
Substance dependence across multiple substances is consistently associated with emotion dysregulation. In the last two decades, emotion regulation interventions have been developed and applied from cognitive behavioral therapy, dialectical behavior therapy, and mindfulness-based interventions for substance dependence.
Recent Findings
While previous reviews have focused solely on cognitive behavioral therapy or mindfulness interventions and have found positive outcomes regarding reductions in substance use, aggregate results of clinical outcomes across different emotion-regulation interventions have not been identified to this date.
Summary
Through our systematic review of 26 studies, our meta-analysis of 10 studies on reduction in substance use, and 11 studies on improvement in emotion regulation outcomes, we found that improved outcomes have been demonstrated across diverse measures from self-report questionnaires to respiratory sinus arrhythmia. Although most emotion-regulation interventions have demonstrated a significant moderate effect size regarding the reduction in substance use and improvement in emotion regulation, mindfulness-based interventions have significantly driven the improvements in emotion regulation. No demographic variables (e.g., age, sex) nor study-design variables (e.g., intervention frequency, intervention length) significantly influenced the reduction in substance use from ER interventions. Our findings demonstrate the importance of cost-effective methods like mindfulness-based interventions towards addressing maladaptive substance use and the broad appeal of emotion regulation interventions to improve the outcomes of individuals afflicted with substance dependence.
Adinazolam (ADZ) is a benzodiazepine-type new psychoactive substance (NPS) with anxiolytic, anticonvulsant, and antidepressant effects. High ADZ doses have been reported to impair psychomotor performance and memory; however, the abuse potential and drug dependence of ADZ have not yet been fully investigated. In this study, we evaluated whether ADZ has abuse potential and leads to drug dependence and withdrawal symptoms. The intravenous self-administration (IVSA) test revealed that ADZ (0.01, 0.03, and 0.1 mg/kg/infusion) was self-administered significantly above vehicle levels, suggesting the reinforcing effect of ADZ. Furthermore, we revealed that treatment discontinuation following chronic ADZ administration (3 and 6 mg/kg) caused several somatic withdrawal symptoms in mice, including body tremor. Moreover, it induced motivational withdrawal signs, such as anxiety-related behavior in the elevated plus maze (EPM) test and memory deficits in the Y-maze test. After the IVSA test, an enzyme-linked immunosorbent assay (ELISA) showed that ADZ administration significantly increased the dopamine contents in the thalamus, nucleus accumbens (NAc), and ventral tegmental area (VTA). This finding was also supported by the results of the Western blot. Taken together, our results suggest that ADZ has abuse potential and can lead to drug dependence and withdrawal syndrome.
Background:
It is unclear whether benzodiazepines increase the risk of suicide. The aim of this study was to test the hypothesis that benzodiazepines are associated with an increased risk of suicide, by comparing psychopharmacological interventions between psychiatric patients who committed suicide and a group of matched controls.
Methods:
The case group comprised 154 psychiatric patients (101 men, 53 women; age range: 13-96 years) who had committed suicide in Örebro County, Sweden. Control psychiatric patients matched by age, sex, and main psychiatric diagnosis were selected for each case. Binary logistic regression was used to calculate odds ratios in unadjusted and adjusted models.
Results:
Benzodiazepine prescriptions were more common among cases than controls (65/154 [42.2%] versus 43/154 [27.9%], p = 0.009, odds ratio: 1.89 [95% CI: 1.17-3.03]). This association remained significant in a model adjusted for previous suicide attempts and somatic hospitalizations (odds ratio: 1.83 [95% CI: 1.06-3.14]). No statistically significant differences were seen between the groups in the use of any other subtype of psychopharmaceutical agent.
Conclusions:
These data indicate that benzodiazepine use may increase the risk of suicide. However, this study is limited by the potential for indication bias.
Objective:
Benzodiazepines (BZDs) are the most commonly prescribed compounds in insomnia. A long-term of BZDs use may cause dependence and abuse. The aim of this study was to evaluate sleep architecture and microstructure (in terms of cyclic alternating pattern - CAP - analysis and of sleep EEG power spectral analysis) in a group of long-term users of high doses of BZDs for their primary chronic insomnia.
Methods:
Twenty patients consecutively admitted at the Sleep Centre for drug discontinuation and 13 matched healthy controls underwent a full nocturnal video-polysomnographic recording, after one adaptation night.
Results:
Significant differences were found in time in bed, REM sleep latency and sleep stage 1% which were increased in patients compared to controls, while CAP rate was dramatically decreased. During NREM sleep, patients showed a clear decrease in the relative power of delta band.
Conclusions:
Our data demonstrate that in adults with chronic insomnia, long-term use of high doses of BZDs induces a severe disruption of sleep microstructure, while sleep architecture seems to be much less affected.
Significance:
The long term use of high doses of BZDs for chronic insomnia induces a marked depression of slow wave activity and of its physiological instability.
Despite the first reports concerning benzodiazepine dependence being published in the early 1960s literature, the risk of benzodiazepine addiction is still greatly debated. The severe discomfort and life threatening complications usually experienced by long-term benzodiazepine users who suddenly interrupt benzodiazepine intake have led to the development of several detoxification protocols. A successful strategy used by our Addiction Unit is abrupt benzodiazepine cessation by administering flumazenil slow subcutaneous infusion (FLU-SSI) with an elastomeric pump. Although some studies proved the efficacy of flumazenil infusion more than 20 years ago, only a few centres in the world offer this method to their patients. This paper reports the data related to 214 subjects addicted to high doses of benzodiazepine and treated with the FLU-SSI method between 2012 and 2014. This technique is less invasive and requires less nursing intervention than intravenous infusion. Our data support FLU-SSI as a possible efficient strategy for the treatment of patients with long-term, high-dose benzodiazepine addiction, and could become a routine therapy as long as the necessary further studies on dose, duration of infusion and safety issues are carried out.
Objectives
This review has the aim of improving early recognition and effective
treatment of catatonia, critically going through its historical
descriptions and revisiting its nosographical collocation in current
classification systems.
Methods
A PubMed search was done using the keywords “catatonia”,
“catatonic schizophrenia”, “stupor”, “catalepsy” and “catatonia
treatment” (until 2011).
Results
In 1874, Kahlbaum first described catatonia as a disease of
its own, characterized by specific disturbances in motor and
behavioural functioning; in contrast, Emil Kraepelin classified
catatonic features as a clinical expression of dementia praecox,
with a chronic course and poor prognosis. Catatonia occurs
in children, adolescents and adults, and develops in association
with a wide variety of psychiatric, neurologic and
general medical conditions. The neurobiological pathways of
catatonia are still unclear. In particular the role of GABA and
other neurotrasmitters has been explored, but not completely
defined. Nosological and diagnostic definition of disorder are
still argued by clinicians and researchers. Although the main
psychiatric classifications continue to sustain Krapelin’s view
of catatonia as a clinical subtype of schizophrenia, in a clinical
setting, catatonic symptoms are more commonly observed in
patients with mood disorders and general medical conditions.
Symptomatology is characterized by a wide array of manifestations:
negativism, mutacism and stupor represent the most
common symptoms. The lack of consensus about diagnostic
criteria often complicates recognition of catatonic symptoms.
The issue in diagnostic assessment is to differentiate catatonia
from other overlapping psychomotor disorders and to identify
the underlying psychiatric and general medical disorders. Early
and correct diagnosis is crucial to start effective treatments and
avoid potentially severe (sometimes lethal) somatic complications.
Benzodiazepines and electroconvulsive therapy are the
therapeutic mainstay for catatonia. Intravenous administration
of BDZ is first-line treatment, where ECT is commonly used
in non-responders to BDZ, malignant catatonia and malignant
neuroleptic syndrome. Nonetheless, many authors suggest that
ECT, preferably in combination with BDZ, should be considered
in the early course of all types of catatonia to improve
prognosis and avoid complications.
Conclusions
Further research should better define the neurobiological basis
and improve clinical and nosographical collocation of catatonia;
evidence-based therapeutic protocols are needed that would allow
adequate and early
Polypharmacy is widely used in the treatment of schizophrenia, although it is believed to have major adverse effects on the well-being of patients.
To investigate if the use of benzodiazepines, antidepressants, or multiple concomitant antipsychotics is associated with increased mortality among patients with schizophrenia.
Registry-based case linkage study.
Academic research.
We linked national databases of mortality and medication prescriptions among a complete nationwide cohort of 2588 patients hospitalized in Finland for the first time with a diagnosis of schizophrenia between January 1, 2000, and December 31, 2007.
Hazard ratios (HRs) were computed for all-cause mortality during the use of antipsychotics, antidepressants, or benzodiazepines in outpatient care, adjusting for the effects of sociodemographic and clinical variables, geographic location, and current and past pharmacological treatments.
Compared with antipsychotic monotherapy, concomitant use of 2 or more antipsychotics was not associated with increased mortality (HR, 0.86; 95% CI, 0.51-1.44). Similarly, antidepressant use was not associated with a higher risk for mortality (HR, 0.57; 95% CI, 0.28-1.16) and was associated with markedly decreased suicide deaths (HR, 0.15; 95% CI, 0.03-0.77). However, benzodiazepine use was associated with a substantial increase in mortality (HR, 1.91; 95% CI, 1.13-3.22), and this was attributable to suicidal deaths (HR, 3.83; 95% CI, 1.45-10.12) and to nonsuicidal deaths (HR, 1.60; 95% CI, 0.86-2.97). In total, 826 of 904 patients (91.4%) who used benzodiazepines had purchased prescriptions that contained more than 28 defined daily doses, violating treatment guidelines.
Benzodiazepine use was associated with a marked increase in mortality among patients with schizophrenia, whereas the use of an antidepressant or several concomitant antipsychotics was not. Antidepressant use was associated with decreased suicide deaths. The literature indicates that long-term use of benzodiazepines among patients with schizophrenia is more prevalent in other countries (eg, the United States) compared with Finland, which suggests that benzodiazepine use may contribute to mortality among this patient population worldwide.
Research on suicide prevention and interventions requires a standard method for assessing both suicidal ideation and behavior to identify those at risk and to track treatment response. The Columbia-Suicide Severity Rating Scale (C-SSRS) was designed to quantify the severity of suicidal ideation and behavior. The authors examined the psychometric properties of the scale.
The C-SSRS's validity relative to other measures of suicidal ideation and behavior and the internal consistency of its intensity of ideation subscale were analyzed in three multisite studies: a treatment study of adolescent suicide attempters (N=124); a medication efficacy trial with depressed adolescents (N=312); and a study of adults presenting to an emergency department for psychiatric reasons (N=237).
The C-SSRS demonstrated good convergent and divergent validity with other multi-informant suicidal ideation and behavior scales and had high sensitivity and specificity for suicidal behavior classifications compared with another behavior scale and an independent suicide evaluation board. Both the ideation and behavior subscales were sensitive to change over time. The intensity of ideation subscale demonstrated moderate to strong internal consistency. In the adolescent suicide attempters study, worst-point lifetime suicidal ideation on the C-SSRS predicted suicide attempts during the study, whereas the Scale for Suicide Ideation did not. Participants with the two highest levels of ideation severity (intent or intent with plan) at baseline had higher odds for attempting suicide during the study.
These findings suggest that the C-SSRS is suitable for assessment of suicidal ideation and behavior in clinical and research settings.
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.
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.
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).
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.
Because use of benzodiazepines may exacerbate existing substance use disorders or become abused substances, prescription of benzodiazepines for patients with severe mental illness (schizophrenia or bipolar disorder) and co-occurring substance use disorders (abuse or dependence) is controversial. The authors examined benzodiazepine use and associated psychiatric, substance abuse, and institutional outcomes in a six-year longitudinal study of patients with co-occurring disorders.
At baseline and yearly follow-up for six years, 203 patients with co-occurring severe mental illness and substance use disorder were prospectively assessed for medication use, substance use, psychiatric symptoms, use of hospitalization, and quality of life.
Almost one-half of the patients (43 percent) reported taking prescribed benzodiazepines at the time of at least one assessment. Patients taking prescribed benzodiazepines were more likely to have high scores on measures of overall symptoms and affective symptoms (anxiety and depression) and low ratings for general quality of life throughout the study. Benzodiazepine use was unrelated to remission of substance use disorder or hospitalization, but a greater proportion of patients who were prescribed benzodiazepines developed benzodiazepine abuse, compared with those who were not prescribed benzodiazepines (15 percent compared with 6 percent).
Prescription benzodiazepine use was common among patients with co-occurring severe mental illness and a substance use disorder and was not associated with any of the measured outcomes other than increasing the likelihood of benzodiazepine abuse. Physicians should consider other treatments for anxiety in this population.
Although it has been claimed that insomnia causes an increased risk for depression, adequate controlled trials testing this hypothesis have not been available. This study contrasted the incidence of depression among subjects receiving hypnotics in randomized controlled trials versus those receiving placebo.
The incidence of depression among patients randomized to hypnotic drugs or placebo was compiled from prescribing information approved by the United States Food and Drug Administration (FDA) and from FDA New Drug Application documents. Available data for zolpidem, zaleplon, eszopiclone, and ramelteon were accessed.
Data for 5535 patients randomized to a hypnotic and for 2318 randomized to placebo were compiled. The incidence of depression was 2.0% among participants randomized to hypnotics as compared to 0.9% among those randomized in parallel to placebo (p < 0.002).
Modern hypnotics were associated with an increased incidence of depression in data released by the FDA. This suggests that when there is a risk of depression, hypnotics may be contra-indicated. Preventive treatments such as antidepressant drugs, cognitive-behavioral therapy, or bright light might be preferred. Limitations in the FDA data prevented a formal meta-analysis, and there was a lack of information about drop-out rates and definitions of depression. Trials specifically designed to detect incident depression when treating insomnia with hypnotic drugs and better summarization of adverse events in trials submitted to the FDA are both necessary.
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High-dose benzodiazepine (BZD) abuse is emerging as a substance use disorder (SUD). The aim of the study is to explore the impact of high-dose lormetazepam (LMZ) abuse and the characteristics of patients affected by this SUD in a tertiary referral addiction unit. We have retrospectively evaluated 1112 patients admitted to the Addiction Medicine Unit, Verona University Hospital, Italy for detoxification from high-dose BZD dependence. LMZ was the most common BZD, with an increasing prevalence from January 2003 to June 2018. Socio-demographic (more women; higher age and education) and clinical features (higher daily diazepam dosage equivalent, BZD abuse duration, age of first BZD intake; BZD prescribed more frequently for sleep disorders; less frequent history of other SUDs, previous/active alcohol, previous opioids abuse; more frequent overall major psychiatric diseases and major depression; less-frequent bipolar disorders and other psychoses, personality disorders, and more than one psychiatric disease) of LMZ vs. other BZD abusers significantly differed. 96.7% LMZ abusers took oral solution, while two-thirds of other BZD abusers took tablets. Oral solution, BZD abuse duration and prescription of BZD for sleep disorders increased, while history of other SUDs, previous/active alcohol and active cannabinoids SUD reduced the risk of high-dose LMZ vs. other BZDs abuse. The large prevalence of high-dose LMZ abusers in Italy may be strongly related to the availability and characteristics of oral formulation that may transform the innocuous Dr. Jekyll tablets into an evil Mr. Hyde. Restriction to the market of LMZ oral formulation might reduce the risk of high-dose abuse.
Given recent attention to emotion regulation as a potentially unifying function of diverse symptom presentations, there is a need for comprehensive measures that adequately assess difficulties in emotion regulation among adults. This paper (a) proposes an integrative conceptualization of emotion regulation as involving not just the modulation of emotional arousal, but also the awareness, understanding, and acceptance of emotions, and the ability to act in desired ways regardless of emotional state; and (b) begins to explore the factor structure and psychometric properties of a new measure, the Difficulties in Emotion Regulation Scale (DERS). Two samples of undergraduate students completed questionnaire packets. Preliminary findings suggest that the DERS has high internal consistency, good test–retest reliability, and adequate construct and predictive validity.
High-dose benzodiazepine (BZD) dependence represents an emerging and under-reported addiction phenomenon and is associated with reduced quality of life. To date there are no guidelines for the treatment of high-dose BZD withdrawal. Low-dose slow flumazenil infusion was reported to be effective for high-dose BZD detoxification, but there is concern about the risk of convulsions during this treatment. We evaluated the occurrence of seizures in 450 consecutive high-dose BZD dependence patients admitted to our unit from April 2012 to April 2016 for detoxification with low-dose slow subcutaneous infusion of flumazenil associated with routine anticonvulsant prophylaxis. In our sample, 22 patients (4.9%) reported history of convulsions when previously attempting BZD withdrawal. Only four patients (0.9%) had seizures during (n = 2) or immediately after (n = 2) flumazenil infusion. The two patients with seizures during flumazenil infusion were poly-drug misusers. The most common antiepileptic drugs (AEDs) used for anticonvulsant prophylaxis were either valproate 1000 mg or levetiracetam 1000 mg. Our data indicate that, when routinely associated with AEDs prophylaxis, low-dose slow subcutaneous flumazenil infusion represents a safe procedure, with low risk of seizure occurrence.
Long-term use of benzodiazepines can lead to dependence. Symptoms of withdrawal include anxiety, irritability, confusion, seizures, and sleep disorders. Withdrawal management relies on the use of a single agent (diazepam) and gradual dose reduction.
Background:
Numerous treatment guidelines recommend that long-term use of benzodiazepines (BZD) should be avoided primarily due to development of tolerance and a risk for BZD dependence. Despite this, long-term BZD use remains a controversial subject in clinical patient care with "for and against" debates. However, there is no explicit understanding of what is meant by long-term BZD use in real world. The aim of this study was to assess different definitions, usage patterns, prevalence and other characteristics of long-term BZD use based on published register-based studies. Synthesis of these characteristics is essential to derive a meaningful definition of long-term BZD.
Methods:
Systematic review of register-based studies on long-term BZD use published in 1994-2014.
Results:
Fourty-one studies met our predetermined inclusion criteria. The length of BZD use defined as "long-term" varied in these studies ranging from one month to several years. The most common definition was six months or longer during a year. The prevalence of long-term BZD use in the general population was estimated to be about 3%. The relative proportion of long-term BZD users (all definitions) in adult BZD users ranged from 6% to 76% (mean 24%; 95% CL 13-36%). The estimates were higher in studies only on the elderly (47%; 95% CL 31-64%). Long-term use involved typically steady treatment with low BZD doses. However, in elderly patients long-term BZD use and exceeding recommended doses was relatively common. Several characteristics associated with long-term use were found.
Conclusions:
Long-term BZD use is common and a clinical reality. Uniform definitions for "long-term", which is in line with population-based evidence, is needed to have more comparable results between studies. Our systematic review suggests that duration of BZD treatment over six months, the most common definition for long-term BZD use in the included studies. As also recommended previously, it is a useful starting point for further analyses on disadvantages but also potential advantages associated with long-term BZD use.
There are well-recognised harms from long-term use of benzodiazepines. These include dependency, cognitive decline and falls. It is important to prevent and recognise benzodiazepine dependence. A thorough risk assessment guides optimal management and the necessity for referral. The management of dependence involves either gradual benzodiazepine withdrawal or maintenance treatment. Prescribing interventions, substitution, psychotherapies and pharmacotherapies can all contribute. Unless the patient is elderly, it is helpful to switch to a long-acting benzodiazepine in both withdrawal and maintenance therapy. The dose should be gradually reduced over weeks to lower the risk of seizures. Harms from drugs such as zopiclone and zolpidem are less well characterised. Dependence is managed in the same manner as benzodiazepine dependence. © 2015, Australian Government Publishing Service. All rights reserved.
The main actions of benzodiazepines (hypnotic, anxiolytic, anticonvulsant, myorelaxant and amnesic) confer a therapeutic value in a wide range of conditions. Rational use requires consideration of the large differences in potency and elimination rates between different benzodiazepines, as well as the requirements of individual patients.
As hypnotics, benzodiazepines are mainly indicated for transient or short term insomnia, for which prescriptions should if possible be limited to a few days, occasional or intermittent use, or courses not exceeding 2 weeks. Temazepam, loprazolam and lormetazepam, which have a medium duration of action are suitable. Diazepam is also effective in single or intermittent dosage. Potent, short-acting benzodiazepines such as triazolam appear to carry greater risks of adverse effects.
As anxiolytics, benzodiazepines should generally be used in conjunction with other measures (psychological treatments, antidepressants, other drugs) although such measures have a slower onset of action. Indications for benzodiazepines include acute stress reactions, episodic anxiety, fluctuations in generalised anxiety, and as initial treatment for severe panic and agoraphobia. Diazepam is usually the drug of choice, given in single doses, very short (1 to 7 days) or short (2 to 4 weeks) courses, and only rarely for longer term treatment. Alprazolam has been widely used, particularly in the US, but is not recommended in the UK, especially for long term use.
Benzodiazepines also have uses in epilepsy (diazepam, clonazepam, clobazam), anaesthesia (midazolam), some motor disorders and occasionally in acute psychoses.
The major clinical advantages of benzodiazepines are high efficacy, rapid onset of action and low toxicity. Adverse effects include psychomotor impairment, especially in the elderly, and occasionally paradoxical excitement. With long term use, tolerance, dependence and withdrawal effects can become major disadvantages. Unwanted effects can largely be prevented by keeping dosages minimal and courses short (ideally 4 weeks maximum), and by careful patient selection. Long term prescription is occasionally required for certain patients.
Background:
Benzodiazepines (BZD) and nonbenzodiazepines hypnotics (z-drugs) are recognized as one of the most widely prescribed medications in the world.
Objectives:
The purpose of the study was to assess the BZD and z-drugs dependence in young to middle-aged outpatients who were taking BZD/z-drugs on a chronic basis, and to characterize their profile.
Methods:
This is a forward-looking cross-sectional epidemiological study. Data were collected through a semi-structured interview within a network of partner pharmacies from the Nantes area, in France. All data were obtained exclusively through patients' declarations. 212 patients (19-64 years old) were included: they were considered dependent when they answered positively to at least three items of the DSM IV. A multivariate logistic regression and a principal component analysis (PCA) were carried out to determine their profile.
Results:
Almost half of the patients met criteria for BZD/z-drugs dependence. The risk to develop BZD/z-drugs dependence is significantly associated with psychiatric history and with the quantity of BZD/z-drugs that is taken. A two factor concept of dependence could be identified according to the PCA: one axis with items of "tolerance" and "long term administration or higher doses", and a second axis with "concerned by treatment" and "somatic consequences". Conclusions/Importance: Among this BZD/z-drug dependent population, the two axes identified in the PCA represent two profiles of dependence: being in positive conditioning or suffering from negative consequences. Clinicians need to know them: these two clinical profiles may have an influence in terms of decision-making, especially to manage discontinuation.
To compare substance use disorders (SUD) treatment patterns and barriers to such treatment among men and women with SUD with and without comorbid major depressive episodes (MDE) in a community sample.
Using data from adult participants in the National Survey on Drug Use and Health 2005-2010, we investigated differences by sex in the association of MDE comorbidity with SUD on patterns of, perceived unmet need for, and the perceived barriers to SUD treatments.
Compared with participants with SUD without MDE, both men and women with comorbid SUD and MDE were more likely to use SUD services or to report an unmet need for such treatment. Sex modified the association of comorbidity and treatment patterns: males with MDE comorbidity had a greater likelihood of emergency room visits and use of inpatient services than females. Barriers to substance treatment were remarkably similar for males and females in both the SUD without MDE group and with MDE group, with attitudinal factors being the most common barriers.
Comorbidity with MDE seems to be an important predictor of service utilization and perceived need for SUD treatment in both men and women. The association of comorbidity with the use of some types of services, however, seems to vary according to sex. The findings have implications for the design of sex-specific SUD treatment programs.
Barriers to both mental health and substance use disorder treatments have rarely been examined among individuals with comorbid mental health and substance use disorders. In a sample of 393 adults with 12-month major depressive episodes and substance use disorders, we compared perceived barriers to these two types of treatments. Data were drawn from the 2005-2011 US National Surveys on Drug Use and Health. Overall, the same individuals experienced different barriers to mental health treatment versus substance use disorder treatment. Concerns about negative views of the community, effects on job, and inconvenience of services were more commonly reported as reasons for not receiving substance use disorder treatment. Not affording the cost of care was the most common barrier to both types of treatments, but more commonly reported as a barrier to mental health treatment. Improved financial access through the Affordable Care Act and parity legislation and integration of mental health and substance use disorder services may help to reduce treatment barriers among individuals with comorbid mental health and substance disorders.
Il Difficulties in Emotion Regulation Scale (DERS) è uno dei test più usati per la valutazione
delle difficoltà nella regolazione emotiva per la popolazione adulta. La versione italiana è stata
somministrata a 190 persone e un sottogruppo (N = 81) ha compilato inoltre una batteria di test
paralleli. I risultati di un’analisi fattoriale confermativa non hanno confermato la struttura originale,
mentre un’analisi fattoriale esplorativa ha indicato sei diverse dimensioni. Lo strumento presenta
buone proprietà psicometriche. Il punteggio totale correla positivamente con l’affettività negativa e
negativamente con quella positiva. L’ansia di tratto è risultata associata al punteggio totale del DERS
e alla scala Difficoltà nella distrazione, mentre la depressione correla con il totale e con le scale
relative alla difficoltà di controllo degli impulsi e di accesso alle strategie di regolazione emotiva. In
conclusione, il test può essere considerato uno strumento utile per misurare le strategie di regolazione
emotiva anche nel contesto italiano.
The Difficulties in Emotion Regulation Scale (DERS) is one of the tests used most frequently to
assess the difficulties in emotion regulation in the adult population. The Italian version of the DERS
was applied to 190 adults, and in addition, a subgroup (81 adults) compiled a series of parallel
tests. The results of a confirmatory factor analysis did not confirm the original structure, while an
exploratory factor analysis indicated six different dimensions of emotion regulation. The tool has good
psychometric properties. The total score correlates positively with negative emotion and negatively
with positive emotion. Trait anxiety was found to be associated with the DERS total score and with the
scale of Distraction difficulties, while depression correlates with the total and with the scales relating
to the difficulty in controlling impulses and accessing the emotion regulation strategies. In conclusion, the DERS can be considered a useful tool to measure the emotion regulation strategies also in the
Italian context.
Benzodiazepines present problems related to both unwanted and withdrawal effects. Dosage adjustments usually obviate unwanted effects except for paradoxical reactions such as hostility. Patients with apparent benzodiazepine dependence need careful assessment with respect to personality, social situation and psychiatric disorder. The patient must be motivated and carefully prepared for withdrawal and taught anxiety management techniques. Withdrawal must always be gradual over at least 6 weeks but very prolonged schedules are counter-productive. Substituting a long-acting for a medium-acting benzodiazepine may be helpful in the more intractable cases. An antidepressant may be needed if a depressive disorder supervenes, but other adjunctive therapies are usually unhelpful.
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 (β = 0.170, P = 0.001) and severity of insomnia (β = 0.145, P = 0.004). Preoccupation was related to anxiety severity (β = 0.194, P = 0.001), antidepressant use (β = 0.197, P < 0.001), alcohol dependence (β = 0.185, P < 0.001) and a higher daily dosage of BZD (β = 0.160, P = 0.001). Lack of compliance was associated with higher age (β = 0.122, P = 0.03), unemployment (β = 0.105, P = 0.04), insomnia (β = 0.129, P = 0.01), antidepressant use (β = 0.148, P = 0.002) and alcohol dependence (β = 0.108, P = 0.02).
Conclusions:
Insomnia, antidepressant use and alcohol dependence may increase the risk of benzodiazepine dependence among individuals who use benzodiazepines.
The aim of this study was to evaluate the reliability and validity of an Italian version of the Difficulties in Emotion Regulation Scale (DERS; Gratz & Roemer, 2004).
Three studies were completed. First, factorial structure, internal consistency, and concurrent validity of our Italian version of the DERS were examined with a sample of 323 students (77% female; mean age 25.6). Second, test-retest analyses were completed using a different sample of 61 students (80% female; mean age 24.7). Third, the scores produced by a small clinical sample of participants (N = 38; mean age = 24.2) affected by anorexia, binge eating disorder, or bulimia were compared to those of an age-matched, nonclinical female sample (N = 38; mean age = 24.7).
The factorial structure replicated quite well the six-factor structure proposed by Gratz and Roemer. The internal consistency and test-retest reliability were adequate and comparable to previous findings. The validity was good, as indicated by both the concurrent validity analysis and the clinical-nonclinical sample comparison.
These studies provide further support for the multidimensional model of emotion regulation postulated by Gratz and Roemer and strengthen the rationale for cross-cultural utilization of the DERS.
Anxiety disorders are frequently under-diagnosed conditions in primary care, although they can be managed effectively by general practitioners.
This paper is a short and practical summary of the World Federation of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) for the treatment in primary care. The recommendations were developed by a task force of 30 international experts in the field and are based on randomized controlled studies.
First-line pharmacological treatments for these disorders are selective serotonin reuptake inhibitors (for all disorders), serotonin-norepinephrine reuptake inhibitors (for some) and pregabalin (for generalized anxiety disorder only). A combination of medication and cognitive behavior/exposure therapy was shown to be a clinically desired treatment strategy.
This short version of an evidence-based guideline may improve treatment of anxiety disorders, OCD, and PTSD in primary care.
Discovered in the late 1950s by Leo Sternbach, the first benzodiazepine (BZD) chlordiazepoxide was followed by several congeners, which rapidly constituted one of the largest and most widely prescribed classes of psychotropic compounds. After 50 years, BZDs are still routinely utilized not only in psychiatry but, more generally, in the whole of medicine. Despite their high therapeutic index which makes BZDs safer than other compounds like barbiturates, as well as their rapidity of onset, psychiatrists and family physicians are well aware about the controversy that surrounds the wide use - often not adequately based on scientific evidence - of BZDs in many psychiatric disorders. In this overview of international treatment guidelines, systematic reviews and randomized clinical trials, the aim was to provide a critical appraisal of the current use and role of BZDs in psychiatric disorders and their disadvantages, with specific emphasis on anxiety and affective disorders, sleep disorders, alcohol withdrawal, violent and aggressive behaviours in psychoses, and neuroleptic-induced disorders. In addition, specific emphasis has been given to the extent of usage of BZDs and its appropriateness through the assessment of available international surveys. Finally, the entire spectrum of BZD-related adverse effects including psychomotor effects, use in the elderly, paradoxical reactions, tolerance and rebound, teratologic risk, dependence, withdrawal and abuse issues was examined in detail.
To re-examine various aspects of the benzodiazepines (BZDs), widely prescribed for 50 years, mainly to treat anxiety and insomnia. It is a descriptive review based on the Okey Lecture delivered at the Institute of Psychiatry, King's College London, in November 2010.
A search of the literature was carried out in the Medline, Embase and Cochrane Collaboration databases, using the codeword 'benzodiazepine(s)', alone and in conjunction with various terms such as 'dependence', 'abuse', etc. Further hand-searches were made based on the reference lists of key papers. As 60,000 references were found, this review is not exhaustive. It concentrates on the adverse effects, dependence and abuse.
Almost from their introduction the BZDs have been controversial, with polarized opinions, advocates pointing out their efficacy, tolerability and patient acceptability, opponents deprecating their adverse effects, dependence and abuse liability. More recently, the advent of alternative and usually safer medications has opened up the debate. The review noted a series of adverse effects that continued to cause concern, such as cognitive and psychomotor impairment. In addition, dependence and abuse remain as serious problems. Despite warnings and guidelines, usage of these drugs remains at a high level. The limitations in their use both as choice of therapy and with respect to conservative dosage and duration of use are highlighted. The distinction between low-dose 'iatrogenic' dependence and high-dose abuse/misuse is emphasized.
The practical problems with the benzodiazepines have persisted for 50 years, but have been ignored by many practitioners and almost all official bodies. The risk-benefit ratio of the benzodiazepines remains positive in most patients in the short term (2-4 weeks) but is unestablished beyond that time, due mainly to the difficulty in preventing short-term use from extending indefinitely with the risk of dependence. Other research issues include the possibility of long-term brain changes and evaluating the role of the benzodiazepine antagonist, flumazenil, in aiding withdrawal.
A prominent media publicity cluster during 2007-2008 in Australia linked the common hypnotic zolpidem to adverse drug reaction reports of parasomnias, amnesia, hallucinations and suicidality. The collection of adverse drug reaction data through spontaneous reporting systems is a mainstay of drug safety monitoring, but a stimulated reporting event such as this often renders such data uninterpretable. As such, we aimed to investigate whether these associations were present before the media cluster and then to quantify the effect of stimulated reporting on those four specific outcomes. Using disproportionality analyses we compared zolpidem to all other drugs in the database, and then separately to each of all hypnotics, then all benzodiazepines, and then temazepam alone, and did so in every year from 2001 to 2008. Year-by-year analyses of Reporting odds ratios for zolpidem exposure and adverse events of interest, adjusted for a number of covariates, revealed an association between zolpidem exposure and parasomnias, amnesia and hallucination both before and after the cluster of media publicity beginning in early 2007. The odds ratios increased significantly after the media publicity for only parasomnias and amnesia. Suicidality was increased in some analyses, but limited data make this outcome difficult to interpret. We conclude that zolpidem adverse drug reaction reports have higher odds for parasomnia, amnesia, hallucination and perhaps suicidality compared to either all other drugs or hypnotics, even before the media publicity cluster. However, the extant literature and the limitations of these spontaneously reported adverse drug reaction data do not allow us to conclude that these events are related causally to zolpidem.
Objective: This paper reviews the potential value in daily clinical practice of an easily applied research tool, the Clinical Global Impressions (CGI) Scale, for the nonresearcher clinician to quantify and track patient progress and treatment response over time.Method: The instrument is described and sample patient scenarios are provided with scoring rationales and a practical charting system.Conclusion: The CGI severity and improvement scales offer a readily understood, practical measurement tool that can easily be administered by a clinician in a busy clinical practice setting.
In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field. There is renewed interest in refined approaches to brain stimulation, particularly for treatment resistant major depressive disorder (MDD).
The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. An evidence-based format was used with updated systematic reviews of the literature and recommendations were graded according to Level of Evidence using pre-defined criteria. Lines of Treatment were identified based on criteria that included evidence and expert clinical support. This section on "Neurostimulation Therapies" is one of 5 guidelines articles.
Among the four forms of neurostimulation reviewed in this section, electroconvulsive therapy (ECT) has the most extensive evidence, spanning seven decades. Repetitive transcranial magnetic (rTMS) and vagus nerve stimulation (VNS) have been approved to treat depressed adults in both Canada and the United States with a much smaller evidence base. There is also emerging evidence that deep brain stimulation (DBS) is effective for otherwise treatment resistant depression, but this is an investigational approach in 2009.
Compared to other modalities for the treatment of MDD, the data based is limited by the relatively small numbers of randomized controlled trials (RCTs) and small sample sizes.
There is most evidence to support ECT as a first-line treatment under specific circumstances and rTMS as a second-line treatment. Evidence to support VNS is less robust and DBS remains an investigational treatment.
The drug therapy of epilepsy evolved enormously in this 50 year period. Advances in therapeutics included the incorporation of pharmacokinetics into clinical practice, enormous advances in neurochemistry, a trend to antiepileptic drug monotherapy, better drug assessment, better understanding of therapeutic outcomes, and the recognition of the large epilepsy treatment gap in many countries. An unprecedented range of new drugs was introduced in this period. Before 1989, these included carbamazepine, valproate, ethosuximide, and the benzodiazepines. Since 1989, 13 more new drugs have been licensed and marketed and there are others in the pipeline. The International League Against Epilepsy and its leading figures have played an important role in these developments. In this period, too, there has been a rapid expansion in research and development within the pharmaceutical industry and a rise in the value of the antiepileptic drug market. In parallel, governmental regulation of pharmaceuticals has greatly increased. To what extent the overall prognosis of epilepsy has improved as a result of these activities is an interesting and perplexing question.
Primary care physicians prescribe the majority of benzodiazepines and thus may see most patients who are dependent on these drugs. The diagnosis of benzodiazepine misuse is based on the history, the physical examination and drug use patterns. The treatment of benzodiazepine misuse can be a challenging process that requires the physician's patience, caution and sound clinical judgment. Patients who misuse benzodiazepines may have coexisting psychiatric problems that require treatment, such as depression or panic disorder. Family physicians can manage these patients but should be prepared to refer them for hospitalization when habituation and withdrawal reactions are complicated by medical instability, noncompliance or clinical deterioration.
Benzodiazepines present problems related to both unwanted and withdrawal effects. Dosage adjustments usually obviate unwanted effects except for paradoxical reactions such as hostility. Patients with apparent benzodiazepine dependence need careful assessment with respect to personality, social situation and psychiatric disorder. The patient must be motivated and carefully prepared for withdrawal and taught anxiety management techniques. Withdrawal must always be gradual over at least 6 weeks but very prolonged schedules are counter-productive. Substituting a long-acting for a medium-acting benzodiazepine may be helpful in the more intractable cases. An antidepressant may be needed if a depressive disorder supervenes, but other adjunctive therapies are usually unhelpful.
The main actions of benzodiazepines (hypnotic, anxiolytic, anticonvulsant, myorelaxant and amnesic) confer a therapeutic value in a wide range of conditions. Rational use requires consideration of the large differences in potency and elimination rates between different benzodiazepines, as well as the requirements of individual patients. As hypnotics, benzodiazepines are mainly indicated for transient or short term insomnia, for which prescriptions should if possible be limited to a few days, occasional or intermittent use, or courses not exceeding 2 weeks. Temazepam, loprazolam and lormetazepam, which have a medium duration of action are suitable. Diazepam is also effective in single or intermittent dosage. Potent, short-acting benzodiazepines such as triazolam appear to carry greater risks of adverse effects. As anxiolytics, benzodiazepines should generally be used in conjunction with other measures (psychological treatments, antidepressants, other drugs) although such measures have a slower onset of action. Indications for benzodiazepines include acute stress reactions, episodic anxiety, fluctuations in generalised anxiety, and as initial treatment for severe panic and agoraphobia. Diazepam is usually the drug of choice, given in single doses, very short (1 to 7 days) or short (2 to 4 weeks) courses, and only rarely for longer term treatment. Alprazolam has been widely used, particularly in the US, but is not recommended in the UK, especially for long term use. Benzodiazepines also have uses in epilepsy (diazepam, clonazepam, clobazam), anaesthesia (midazolam), some motor disorders and occasionally in acute psychoses. The major clinical advantages of benzodiazepines are high efficacy, rapid onset of action and low toxicity. Adverse effects include psychomotor impairment, especially in the elderly, and occasionally paradoxical excitement. With long term use, tolerance, dependence and withdrawal effects can become major disadvantages. Unwanted effects can largely be prevented by keeping dosages minimal and courses short (ideally 4 weeks maximum), and by careful patient selection. Long term prescription is occasionally required for certain patients.
This study aimed to evaluate the concurrent and lifetime psychiatric comorbidity and drug use patterns in patients admitted to the hospital for detoxification from benzodiazepines. Psychiatric assessments using the Structured Clinical Interview for DSM-III-R with a psychosis screening module (SCID-P and II) were conducted in 30 inpatients admitted to the medical unit treatment unit of the Clinical Research and Treatment Institute of the Addiction Research Foundation for the treatment of severe benzodiazepine dependence. Patients (mean age, 36 years; range, 22-58; number of DSM-III-R criteria met for benzodiazepine substance dependence, > or = 7 out of 9 [73%], all 9 criteria [40%]) used benzodiazepines and other drugs over prolonged periods of time at high doses, and their daily functioning was substantially impaired (Mean Global Assessment of Functioning Score, 48; range, 31-60). The most common lifetime psychiatric diagnoses were major depression (33%), other psychoactive drug dependence (100%) (opioids, 77%; alcohol, 53%), and panic disorder (30%). Current psychiatric diagnoses in addition to benzodiazepine dependence included other psychoactive substance use disorders (83%) (opioids, 67%; cocaine, 13%; multiple concurrent substance use, 17%), panic disorder (13%), and generalized anxiety disorder, (20%). Personality disorders included antisocial (42%), avoidant (25%), and borderline (17%). These findings demonstrate that in patients severely dependent on benzodiazepines, additional psychoactive substance use and mental disorders are prominent. The pattern of drug use and psychiatric comorbidity differentiates these patients from therapeutic-dose benzodiazepine users.
The high rate of co-occurrence of substance use disorders and other psychiatric disorders is well established. The population of people with co-occurring disorders is heterogeneous, and the prevalence of comorbidity differs by diagnostic group. One of the overarching issues in the area of comorbidity is the nature of the connection between psychiatric disorders and substance use disorders. The rapid development of technical advances in the neurosciences has led to a better understanding of the molecular biology, neurotransmitter systems, and neural circuitry involved in mental illness and substance use disorders. The authors discuss the neurobiological interface between substance use disorders and other psychiatric disorders with an emphasis on emerging data concerning four psychiatric disorders that commonly co-occur with substance use disorders: depression/mood disorders, posttraumatic stress disorder, attention deficit hyperactivity disorder, and schizophrenia. Better understanding of the connection between substance use disorders and psychiatric disorders could have a profound effect on prevention and treatment.
BACKGROUND: Benzodiazepines have many benefits for persons with severe mental disorders, but they may also lead to or exacerbate substance abuse. An American Psychiatric Association taskforce established practice guidelines in 1990 to assist physicians in managing these and other potential side effects of benzodiazepine use. The objectives of this study were to determine the prevalence of benzodiazepine use among persons with psychiatric disorders and to evaluate compliance with published prescribing guidelines.
METHOD: We studied benzodiazepine use among New Hampshire Medicaid beneficiaries aged 18 to 64 years with ICD-9 diagnoses that were grouped under the headings "schizophrenia," "bipolar disorder," "major depression," and "other psychiatric disorders" from Jan. 1995 through Dec. 1999. Rates and length of use, frequency of high-potency/fast-acting prescriptions, and diazepam-equivalent dosages were compared for those with and without retrospectively determined evidence of substance abuse, substance dependence, or a procedure code indicating treatment for a substance use disorder (SUD).
RESULTS: Five-year prevalence of benzodiazepine use for persons with and without SUD was 63% versus 54% for schizophrenia, 75% versus 58% for bipolar disorder, 66% versus 49% for major depression, and 48% versus 40% for other psychiatric disorders. Differences were statistically significant over 5 years and in 1999 (p
The frequency of sleep disruption and the degree to which insomnia significantly affects daytime function determine the need for evaluation and treatment. Physicians may initiate treatment of insomnia at an initial visit; for patients with a clear acute stressor such as grief, no further evaluation may be indicated. However, if insomnia is severe or long-lasting, a thorough evaluation to uncover coexisting medical, neurologic, or psychiatric illness is warranted. Treatment should begin with nonpharmacologic therapy, addressing sleep hygiene issues and exercise. There is good evidence supporting the effectiveness of cognitive behavior therapy. Exercise improves sleep as effectively as benzodiazepines in some studies and, given its other health benefits, is recommended for patients with insomnia. Hypnotics generally should be prescribed for short periods only, with the frequency and duration of use customized to each patient's circumstances. Routine use of over-the-counter drugs containing antihistamines should be discouraged. Alcohol has the potential for abuse and should not be used as a sleep aid. Opiates are valuable in pain-associated insomnia. Benzodiazepines are most useful for short-term treatment; however, long-term use may lead to adverse effects and withdrawal phenomena. The better safety profile of the newer-generation nonbenzodiazepines (i.e., zolpidem, zaleplon, eszopidone, and ramelteon) makes them better first-line choices for long-term treatment of chronic insomnia.
The misuse of benzodiazepines among high-risk opioid users in Europe
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