Do Benzodiazepines Cause Depression
Misconceptions involving benzodiazepines being produced to treat depression are common. Considering the benzodiazepine depression relationship, it is reasonable to question if benzodiazepines not only help with depression but also if they can cause depression.
Research has shown that people with pre-existing depression or a predisposition to depression are more likely to experience a depressive episode or increase existing levels of depression induced from the use of benzodiazepines.
The Search Strategy And Quality Of Evidence
The review authors examined only the highest levels of individual study evidence: randomised controlled trials, including the relevant arms of cross-over studies. To maximise the systematic nature of the search, they searched the Cochrane Common Mental Disorders Group’s Controlled Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, the World Health Organization trials portal, ClinicalTrials.gov and reference lists, and contacted principal investigators to identify any additional unpublished or ongoing studies, with no restrictions for language. Despite this very comprehensive strategy, from inception to May 2019, no new data emerged as published after 2002. It is perhaps surprising that no new studies were found since the 2005 update . However, this might indicate that clinical practice may recently have moved away from the use of benzodiazepines in general owing to the concerns about iatrogenic harm, most particularly fostering dependence.
The authors used the GRADE criteria to evaluate the quality of the evidence this was one of the updates they made to the review methods used in the 2005 version. Bias was classified as unclear from examining the reports of most studies, probably because many of the studies included date from a time when reporting guidelines were less prevalent, and no studies had an available protocol .
BOX 2 Study protocols
BOX 3 Attrition bias
Does Xanax Help With Or Cause Depression
Some doctors prescribe alprazolam to treat anxiety disorders like panic disorder and generalized anxiety disorder. This medication can provide short-term relief for panic attacks and other symptoms of anxiety.
Many people who suffer from anxiety also struggle with depression. If youre one of them, you may wonder how Xanax will impact your depressive symptoms.
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Who Should Avoid Taking Benzodiazepines
Your doctor will not normally prescribe you benzodiazepines if you have:
- severe lung disease or breathing problems
- sleep apnoea
- severe liver or kidney disease
- severe and uncontrolled myasthenia gravis .
Your doctor may be cautious about offering you benzodiazepines if you have:
- chest and lung problems
- a diagnosis of personality disorder.
Your doctor should prescribe a reduced dose of benzodiazepines if you have:
- liver or kidney problems
- porphyria
Whether you are prescribed benzodiazepines may also depend on your age:
- Benzodiazepines are not suitable for children. This is except for rare cases of anxiety or insomnia caused by fear or sleepwalking, when diazepam may be prescribed.
- Older people should be given a lower dose than the standard adult dose.
If you have any medical conditions or are receiving any other treatments, let your doctor know. This includes any conditions which arent listed here.
They can help you decide whether or not it is safe for you to take this medication.
Weak External Evidence In Light Of Changing Prescribing Practices
The major problem with the external validity of this review update is the lack of recent evidence. Many of the background references used in the review were published before 2000, which likely relates to the age of the original review. This is in line with a lack of included studies in the review since the last update in 2005 , indicating that the evidence in this field has not substantially changed in the past 1520 years. However, clinical practice in psychiatry has changed significantly even since the most recently published study in 2002. A large epidemiological study identified that the proportion of patients with concurrent new antidepressant and benzodiazepine use increased from 6.1% in 2001 to 12.5% in 20122014 . This is concerning considering the apparent lack of data regarding longer-term outcomes for the combination of benzodiazepines and antidepressants, alongside the potentially positive data regarding short-term use of this combination therapy. Considering the conclusions of this Cochrane review, it is possible that any clinical benefit of benzodiazepines as an adjunct in depression is limited to very early use, but this is not yet clear from the randomised data included.
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Tolerance Dependence And Withdrawal
Benzodiazepines have the potential for physical dependence when used for long periods of time, especially at high doses. They can also be psychologically addictive in some individuals.
Studies have shown that people who take benzodiazepines over a long period of time may develop tolerance that reduces the therapeutic benefits. If tolerance occurs, larger doses of benzodiazepines may be needed to bring about desired results.
Long-term use of benzodiazepines may result in physical dependence and withdrawal symptoms if the medication is stopped or decreased suddenly. Withdrawal symptoms may include:
- Tremors
- Seizures
Do not discontinue or decrease your benzodiazepine medication without consulting your doctor. It may be necessary to decrease your dosage slowly to avoid withdrawal complications.
Types Of Benzodiazepines For Anxiety
Common uses for benzodiazepines include the treatment of anxiety, panic attacks, and insomnia. Examples of benzodiazepines used for the treatment of anxiety-related to panic disorder or other anxiety disorders include:
- Xanax : Prescribed for short-term relief of anxiety symptoms
- Klonopin : Prescribed to treat panic disorder and panic attacks
- Valium : May be prescribed during the initial phase of treatment for panic disorder
- Ativan : May be prescribed to treat anxiety symptoms that occur with other psychiatric conditions
- Librium : May be used to treat anxiety disorders as well as alcohol withdrawal
Benzodiazepines may also be prescribed for other conditions including seizures, muscle spasms, and withdrawal from alcohol or other drugs. They may also be used to treat sleep disorders and to induce a relaxed state prior to surgery.
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Strategy No : Assess And Manage Ssri
When directly questioned by a physician, about 60 percent of patients who take SSRIs report experiencing sexual dysfunction, including delayed orgasm, anorgasmia, loss of libido, decreased lubrication, and erectile dysfunction11 that number drops to 14 percent when patients spontaneously report the information.12 Only 25 percent of these patients with sexual dysfunction report being able to tolerate this side effectpresenting a major challenge because of the long-term nature of the treatment.12
In general, the sexual dysfunction is dose-related and responds to reductions in the total amount of antidepressant medication used.11,12 Occasionally, patients can successfully alter the time of dosing or skip doses prior to sexual activity. This strategy would presumably work best with short half-life agents such as paroxetine or sertraline .11 Because sexual dysfunction is ordinarily a class effect, switching SSRIs is usually not beneficial. Unfortunately, venlafaxine has an incidence of sexual dysfunction similar to that of conventional SSRIs.11
Antidepressants Plus Benzodiazepines For Major Depression
Why is this review important?
Major depression is characterised by depressed mood, loss of interest or pleasure, diminished energy, fatigue, difficulties with concentration, changes in appetite, sleep disturbances and morbid thoughts of death. Depression often presents with anxiety. Depression and anxiety have negative impacts on the person and on society, often over the long term.
Who will be interested in this review?
Health professionals, including general practitioners and psychiatrists people with major depression and the people around them.
What question does this review aim to answer?
Major depression is often treated by combining antidepressant drugs with benzodiazepines. Benzodiazepines are a family of anxiety-reducing and hypnotic drugs. This review asked if combined antidepressant plus benzodiazepine treatment, compared with antidepressants treatment alone, had an effect on depressive symptoms, rates of recovery and the acceptability of these treatments based on the number of people who left the study early , in adults with major depression.
Which studies were included in the review?
We searched electronic databases to find all relevant studies in adults with major depression. To be included, the studies had to be randomised controlled trials , which means adults were allocated at random to receive either antidepressants plus benzodiazepines or antidepressants alone .
What does the evidence from the review tell us?
What should happen next?
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Side Effects And Concerns
Anyone who chooses to take a benzo, whether prescription or not, must take extreme caution. These are sedatives, which means they slow your brain and body down. They can make you drowsy, confused, and dizzy. They can impair your motor skills, or even lead to depression. Thats right, not only can stopping the medicine cause depression, but using them can actually cause depression too. There are risks in both directions and depression and fatigue are among the least concerning effects believe it or not.
On the more serious side of the spectrum, Benzodiazepines can erode memory. They can cause extreme fatigue, delirium, and agitation. Some more severe physical symptoms include tremors, shortness of breath, and gastrointestinal issues. They can also cause psychological symptoms like hallucinations and delusions. These effects are all limited to the time when youre actually taking these medications. The more extreme examples are typically only seen with misuse, but the milder effects can occur under normal, prescribed use and are still concerning.
Benzodiazepine Dependence And Future Research
Dependence is a common concern with benzodiazepines , but there is little evidence regarding this in the review, which is important when considering the clinical applicability of its findings. Despite the potential positive findings in terms of combination therapy and a reduction in early depression severity in this review, it remains difficult to know whether clinicians should consider adding a benzodiazepine to an antidepressant acutely if we are unclear about the potential harms of dependence with such an intervention.
The authors suggest that longer-term trials with a pragmatic design are required to improve the current evidence base, particularly in terms of the potential for benzodiazepine dependence and withdrawal for short- and longer-term prescriptions. As the authors acknowledge, only one included study followed up individuals for longer than 8 weeks and could be included in the longer-term assessment of combination treatment. High drop-out rates were a major problem for most of the included trials and would be worth further exploring. This was reported in the review’s discussion but less so in its summary.
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Strategy No : Use A Rational Sequence Of Treatments
Selecting treatments for panic disorder in a rational sequence will presumably decrease the likelihood of a patient becoming refractory to treatment. Several groups2,17,27 have proposed guidelines for treatment selection but, except for a general preference to begin with an SSRI or CBT, the recommendations differ. Unfortunately, there are no controlled trials to guide the next therapeutic selection.18 The recommendations of these groups and the authors clinical experience are synthesized in the algorithm presented in Figure 1.2,18,27
Augmentation, the addition of another treatment to a partially effective maintenance drug program, has become popular in the treatment of panic disorder.1 Buspirone, beta blockers, and bupropion have all been shown to be ineffective as monotherapy anecdotal evidence supports their use for augmentation. TCAs, benzodiazepines, valproate , and CBT may also add benefits to SSRI therapy.1 Guidelines for the use of augmentation strategies are shown in Table 2.1,5,10,28 Because of drug interactions and the potential for side effects and other complexities, a referral to a psychiatrist should be considered before undertaking augmentation.
| Strategy |
|---|
From Barbiturates To Benzos
Nothing is more tormenting to a melancholic than to lie awake for several hours in the early morning, alone with his morbid thoughts and his intense desire for the peace of sleep. Judicious prescription of the proper dosage of the right drug is most rewarding to such a patient.That was from Frank Ayds 1961 textbook Recognizing the Depressed Patient, and the right drug he was talking about was the barbiturates. Soon after the books release, barbiturates were replaced with the benzodiazepines, and the benzos were later supplanted by the z-hypnotics, at least for sleep. It sounds like progress, but we arent too far from Dr. Ayds world. All of these drugs are gaba-ergic, and their main difference is in safety, not efficacy. In fact, the older versions are arguably more potent than the newer gaba-ergics we use today. But they were also more toxic and more addictive. Barbiturates were fatal in overdose on their own while benzos mainly cause overdose deaths when combined with other drugs like opioids or alcohol. The Z-hypnotics have been with us since the late 1980s, and were still debating whether they lead to dependence or significant overdose problems.
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Treating Depression And Anxiety With The Benzodiazepine Alprazolam: New Cochrane Review Recommends Caution
Antidepressants and psychotherapies are the mainstay for treating depression, but another option is the benzodiazepine drug alprazolam, which is recommended for treating depression when anxiety is also involved.
Some doctors prescribe a short course of benzodiazepines to help depressed and anxious patients, but this is not supported by NICE guidance. High-potency tranquillisers like alprazolam are thought to have side-effects including dependence, rebound anxiety, memory impairment, accident-proneness and discontinuation syndrome.
A new systematic review from the Cochrane Depression, Anxiety and Neurosis Group suggests that alprazolam may be as effective as antidepressants in treating depression, but the authors urge caution because of the quality of the studies included in their review.
They conducted the usual systematic Cochrane search looking for randomised controlled trials of alprazolam versus placebo or conventional antidepressants for depression in adults, excluding studies with inpatients only. Their search included all RCTs published up until February 2012 and they did not apply any language restrictions.
They found 21 RCTs including a total of 2,693 patients. Typical study duration was 4-6 weeks and 6 of the included studies had a high risk of bias.
Two authors from their team carried out independent data extraction and assessed the quality of the included research, to ensure that their interpretation of the evidence was accurate.
Adjunctive Benzodiazepines In Depression: A Clinical Dilemma With No Recent Answers From Research
- Angharad N. de Cates*
- Affiliation:Wellcome Trust Doctoral Training Fellow in the Department of Psychiatry, University of Oxford, and an Honorary Specialist Registrar with Oxford Health NHS Foundation Trust, UK. She is also the RCPsych Neuroscience Champion for the West Midlands.
- Riccardo De Giorgi
- Affiliation:Wellcome Trust Doctoral Training Fellow in the Department of Psychiatry, University of Oxford, and an Honorary MRCPsych Clinical Fellow with Oxford Health NHS Foundation Trust, UK. Both authors work on experimental medicine studies for mood disorders and have interests including the evidence-based treatment of mental illness and the neuroscientific underpinnings of psychopharmacology.
- *
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While Not Typically An Indicated Use Benzodiazepines For Depression Have Become More Common
Benzodiazepines also referred to as benzos, are a class of medications used for their relaxing properties. Benzodiazepines are most commonly prescribed to treat anxiety disorders, insomnia, seizures and as a sedative prior to surgery. While not typically an indicated use, benzodiazepines for depression have become more common.
As many as 40 percent of patients with a depressive disorder may be prescribed benzodiazepines as treatment. When examining the relationship between benzodiazepines and depression treatment, studies have not found a connection between the severity of depression and the use of benzodiazepines.
However, it appears the symptom is known as anhedoniaor loss of pleasureis an indicator of whether benzodiazepines will be prescribed for depression treatment. Other common conditions that are prescribed a benzodiazepine prescription for depressive disorders include insomnia and depression-related anxiety. Despite studies showing that benzodiazepines are not necessarily more effective than placebos for treating depressive disorders, they continue to be used.
How Benzodiazepines Work
Benzodiazepines increase the production of the neurotransmitter gamma aminobutyric acid . GABA is a chemical that slows down processing within the brain. The primary effects are a sense of calm and well-being. When the brain has insufficient GABA, this can lead to anxiety disorders and panic attacks. Taking these medicines as prescribed can alleviate these symptoms.
Increases in GABA also seem to alleviate seizures and high blood pressure. The problem is that benzo medications are inherently habit forming. Not only does the sense of calm and well-being sometimes entice people into abusing these medications looking for a high, but regular use even following a prescription can and often does lead to physical dependence.
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Less Is More Approach
When it comes to depression or anxiety, health care providers wont automatically reach for the prescription pad as if it were an infection that required antibiotics. Many times, theyll try non-medicinal approaches first and rely on medication when necessary.
Providers may recommend non-pharmacological recommendations or lifestyle modifications to address the anxiety or depression disorders. Increasing physical activity, relaxation technique such as deep breathing exercises are a couple of ways to reduce stress and anxiety levels and improve mood.
At first, we like to ask, Can we treat without medication? Pho said. A provider might recommend cognitive behavioral therapy, group therapy or other non-pharmaceutical approaches for initial recommendations and referral to psychiatry clinic for evaluations and assessments.
All medications come with a chance of side effects, and taking more and more medication can have increasing side effects or adverse reactions to other medications and increase risks of potential harmful drug interactions. However, in many cases, medication is required.
Depression and anxiety are both mental illnesses, and if there is a medical reason, or evidence how the disorder effects patients quality of life or living, medication therapy can provide the care and help needed. Together with the patients as a team, provider will weigh the risks and benefits with each medication therapy.