The most common side effects of benzodiazepines are drowsiness, light-headedness, disorientation, unsteadiness, dizziness, slurred speech, muscle weakness, and memory issues. Other side effects include anxiety, depression, and insomnia.
In this article, we will dive more into the side effects of benzodiazepines, so if you wish to learn more, just keep on reading.
Clinical uses of benzodiazepines
Generalized Anxiety Disorder (GAD) is a frequent issue in adults; however, when persistent, unnecessary concern lasts for a period of six months or more and interferes with regular everyday activities, it may be classified as a medical condition (GAD).
GAD is the most common of the types of anxiety disorders, affecting 6.8 million individuals in the United States, or around 3 percent of the general population, with more than half of those affected going untreated. It may be quite frequent in people over the age of 65.
The most common anxiety symptoms of GAD include anxiety that has been present for at least six months and has not been caused by another mental illness, medicine, or irritation and irritability due to muscular stress, sleep difficulties, sleeplessness, and exhaustion.
The amount of anxiety, the patient’s age and organ function, and the patient’s preferences will all influence the choice of medication. Cognitive-behavioral therapy and relaxation treatment have both been demonstrated to be useful for individuals who do not want to take medication; nevertheless, it is possible that a combination of the two will be most successful. Exercise on a daily basis has been demonstrated to be beneficial for many people suffering from anxiety disorders.
In most patients, antidepressants (SSRIs/SNRIs) are considered first-line therapy, while benzodiazepines may be used as adjuvant therapy in the treatment of generalized anxiety disorder (GAD) to alleviate immediate symptoms until the antidepressant takes action. Low-dose benzodiazepines should only be used for a limited period of time (2 to 6 weeks), with a gentle, progressive tapering down after the antidepressant effect has been established. Concerns concerning the hazards of tolerance, dependency, and diversion with benzodiazepines restrict its efficacy in the treatment of generalized anxiety disorder (GAD). It is recommended that benzodiazepines be avoided in patients who have a history of drug dependence.
Because of the potential of severe sedation, disorientation falls, and fractures in the elderly, benzodiazepines should be taken with great care in this population.
The benzodiazepine hypnotics reduce the amount of time it takes to fall asleep and increase the amount of time spent sleeping. The most significant variations occur in the length of time they may stay in the body, potentially resulting in persistent negative effects.
For example, lorazepam has a much shorter duration of action than diazepam, allowing for faster clearance of the medication and, thus, potentially fewer adverse effects. Diazepam, on the other hand, may linger in the system for many days, increasing the risk of long-term negative effects, particularly in the older population.
In the case of insomnia and sleep disorders, benzodiazepines should only be administered for a brief length of time (typically 2 to 4 weeks).
Short-acting benzodiazepines are often used to treat insomnia since they are thought to induce less next-day drowsiness, yet many patients still have similar side effects after using these medications.
On the whole, people should reevaluate their sleeping patterns: avoid drinking caffeinated beverages at night and avoid using gadgets in the bedroom or within 1-2 hours before bed. They should also avoid consuming alcohol late in the day.
Exercise performed early in the day may typically aid in the promotion of more peaceful sleep; yet, exercise performed late at night may be stimulating and have the opposite impact on sleep.
Because of the availability of newer nonbenzodiazepine drugs, such as eszopiclone (Lunesta), zolpidem (Ambien), and zaleplon (Zaleplon), the older benzodiazepines that were initially approved by the FDA for insomnia, such as temazepam (Restoril) and triazolam (Halcion), are not used as frequently as they were in the past (Sonata). Every one of the nonbenzodiazepine agents has a limited indication: they are all licensed for the treatment of insomnia.
Withdrawal from alcohol
Patients suffering from alcohol withdrawal are often those who have had severe and continuous alcohol use, as well as those who have experienced a rapid decrease or full abstinence from alcohol. Alcohol withdrawal symptoms include physiological changes in the body, including, tremors or shakiness, difficulty sleeping, confusion, anxiety, hallucinations, seizures, and delirium.
When it comes to acute alcohol withdrawal, medications such as benzodiazepines are the first line of defense because of their effectiveness at addressing withdrawal symptoms as well as addiction treatment.
Benzodiazepines help patients cope with withdrawal symptoms and may even save their lives in certain cases. Among the most often prescribed medications to ease withdrawal symptoms in this category are chlordiazepoxide (Librium), diazepam (Valium), and lorazepam (Ativan).
In individuals with liver disease such as cirrhosis, lorazepam (Ativan) or oxazepam (Serax) may be preferable above other medications. In addition to oral administration, chlordiazepoxide, diazepam, and lorazepam may also be administered intravenously or intramuscularly. Oxazepam may be beneficial, however, it is only accessible as an oral medication.
Panic disorders are classified as a type of anxiety disorder. In the United States, around 6 million individuals, or 2.7 percent of the general population, are afflicted by the disease. Panic attacks, which are recurring periods of great terror that may be predicted or unexpected, are experienced by those who suffer from panic disorder.
Symptoms comparable to those associated with the body’s natural reaction to danger, known as the “fight or flight” phenomenon, may be present in conjunction with these signs and symptoms. Panic attacks may occur in conjunction with other mood disorders, such as sadness, anxiety, or drug addiction problems, among other things.
Symptoms of a panic disorder include increased heart rate, flushing, redness, sweating, shortness of breath, a feeling of dread and increased awareness of surroundings, even if no threat is apparent, concern about death or losing control, avoidance of crowds or other public settings, owing to the apprehension of an imminent attack are all symptoms of panic disorder.
To treat people who do not have co-existing problems such as depression or a history of drug misuse, benzodiazepines may be taken carefully and temporarily for a short amount of time.
While antidepressants are taking effect, which may take 4 to 6 weeks, benzodiazepines may be used to alleviate symptoms during the first few weeks of the treatment. Anxiety attacks may be alleviated with the use of benzodiazepines such as clonazepam (Klonopin), lorazepam (Ativan), diazepam (Valium), and alprazolam (Xanax). When taken as indicated, they are completely safe and may sometimes provide immediate relief from panic symptoms.
When benzodiazepines are stopped, they should be weaned down gradually to minimize withdrawal symptoms such as sleeplessness and anxiety. There is a significant danger of misuse, dependency, and overdose with benzodiazepines, which is its principal drawback (especially with opiates). The selection of medication treatment should be based on factors such as dose, potential adverse effects, or drug interactions, as well as price and availability.
When the component of muscle relaxation is required, the skeletal muscle relaxant family of drugs, which includes medicines such as baclofen, carisoprodol (Soma), methocarbamol (Robaxin), metaxalone (Skelaxin), and cyclobenzaprine (Amrix), is often employed first.
Benzodiazepines, such as diazepam, may also be used as a muscle relaxant for a brief period of time. The majority of the time, they are utilized to alleviate acute painful skeletal muscle spasms, such as those that may occur with an acute lower back muscular spasm. They are used in conjunction with other treatments such as rest, physical therapy, and/or heat and ice.
Conscious sedation or procedural sedation
Pre-operative or intraoperative sedation is the administration of a combination of drugs in order to assist the patient to relax and blocking discomfort during medical or dental treatment. Benzodiazepines, such as diazepam or midazolam, are often used for anxiety disorders.
A common application of this method of sedation is in the setting of outpatient surgery or procedures that allow patients to return home the same day. Examples include endoscopy or colonoscopy procedures, wisdom tooth extraction, biopsies, and uncomplicated surgical procedures that last less than one hour.
In most cases, there is no need to assist breathing when under conscious sedation; nevertheless, a deeper degree of sedation may sometimes occur, and as a result, respiratory and resuscitative equipment should always be readily accessible to healthcare professionals.
The duration of action of the benzodiazepines most typically used for procedural sedation is classed as follows: diazepam is regarded to be the longest acting, while midazolam is considered to be the shortest acting. There are no analgesic characteristics associated with them.
When performing operations that are anticipated to take less than an hour, midazolam is routinely utilized, and it may be coupled with the opioid fentanyl to provide pain relief.
Patients who are old or obese, as well as those who have liver disease, may have a longer sedative effect.
The patient may be awake but drugged throughout the surgery, and he or she will likely have no recall of it. The majority of patients are able to react to verbal or physical stimuli. This sort of sedation permits the patient to recover from anesthesia more rapidly than with other types of sedation. They will need transportation home and will be sleepy till the following day, necessitating the need to take a full day off from work.
Benzodiazepines are often used in the treatment of seizures – examples include clobazam, clonazepam, clorazepate, diazepam, lorazepam, and midazolam
For most types of acute or prolonged seizures or status epilepticus, an intravenous (IV) or rectal benzodiazepine would be the treatment of the first choice.
Status epilepticus is considered a medical emergency in which there are either more than 30 minutes of continuous seizure activity, or there are two or more sequential seizures without recovery of full consciousness between two seizures.
Intravenous lorazepam is considered to be the first treatment of choice by many clinicians. Diazepam is available as a rectal gel for patients without access to an IV line. Midazolam is often selected for intramuscular (IM) or oral therapy.
Clonazepam is the benzodiazepine most frequently used for long-term control and prevention of chronic seizure disorders; however, in general, benzodiazepines are not usually the first choice for seizure prevention.
Benzodiazepines are not appropriate for the long-term control of epilepsy because of the development of tolerance in a high proportion of patients. More traditional types of seizure treatments might be used first-line, dependent upon patient characteristics and specific epilepsy diagnosis.
Lennox-Gastaut syndrome is a severe form of epilepsy that usually begins in early childhood and also causes developmental and behavior problems. This form of epilepsy may involve seizures of multiple types, mental impairment, and a particular brain wave pattern. Clobazam is used as an add-on benzodiazepine anticonvulsive treatment with other seizures medications in the treatment of Lennox-Gastaut syndrome.
Toxicity and side effects
Potency and half-life of various benzodiazepines
Some benzodiazepines have a longer duration of action on your brain and body than others. In order to understand how long a drug’s effects may persist, it is necessary to know how long its half-life is.
Short-acting benzodiazepines have a shorter half-life than long-acting benzodiazepines. This implies that the medications are metabolized and eliminated from your system more rapidly. Short-acting medications are associated with an increased chance of experiencing withdrawal symptoms. This is due to the fact that your body has less time to adjust to functioning without the medicine once you stop taking it.
Long-acting benzodiazepines have a longer half-life than short-acting benzodiazepines. This implies that the medications are metabolized more slowly by your body and so take longer to exit your body when you take them. Take these medications and you are more likely to suffer a “hangover” effect as a result. However, you are less likely to have withdrawal symptoms.
Short-acting benzodiazepines are often used as sleeping medicines, but long-acting benzodiazepines are typically used to treat anxiety. This, however, is not always the case. If you take some anxiety medications at night, you may find that they help you sleep better. Additionally, if you use sleeping drugs during the day, lesser amounts may help you feel more tranquil.
Benzodiazepines may be classified according to their potency. This has everything to do with the potency of the chemical response that each medicine creates in your body, as explained above.
Take a lesser dosage of a high-potency benzodiazepine, and the effects may be comparable to those of a greater dose of a low-potency benzodiazepine, according to the manufacturer.
It is believed that the body breaks down benzodiazepines in many ways. The process through which your body metabolizes the medicine is known as pharmacokinetics.
In the course of their metabolism, several benzodiazepine medications, such as diazepam, create a number of other benzodiazepine compounds. These extra substances remain in your system for a longer period of time, extending the total duration of the drug’s action.
Drug interactions and toxicity
Because many drug interactions may occur with benzodiazepines, having a drug interaction screen conducted by a medical professional is a crucial step every time a new medicine is introduced or a medication is withdrawn from a treatment program.
When traditional benzodiazepines are taken with alcohol, opioids, other sedatives, or illegal narcotics, they may result in high doses and catastrophic effects. While high doses of benzodiazepines by themselves are very unlikely to be deadly, when taken with other medicines that depress the central nervous system, the danger rises considerably.
The following are examples of various medications that, when coupled with benzodiazepines, may increase the severity of central nervous system depression: phenothiazines, opioids, barbiturates, monoamine oxidase (MAO) inhibitors, sleeping pills, antidepressants, alcohol, and illegal drugs such as heroin are all examples of substances that are addictive.
Consecutive use of or when you abuse benzodiazepines and opioids, as mentioned in the Boxed Warnings, has been shown to cause deep drowsiness, cognitive decline, cognitive impairment, respiratory depression, coma, and death in certain cases.
A large number of conventional benzodiazepines are degraded in the liver, and when they are taken with medications that inhibit this breakdown, blood levels might increase, resulting in negative effects. Because they have fewer liver enzyme interactions, lorazepam, oxazepam, and temazepam are less prone to cause this problem.
However, there are several more possible interactions, necessitating the use of a medication interaction screen with your pharmacist or physician. Patients should not abruptly discontinue the use of any drugs, including benzodiazepines, without first consulting their healthcare provider. It is possible to have significant withdrawal symptoms if you stop using benzodiazepines too soon.
In most cases, patients suffering from benzodiazepine toxicity will present with central nervous system depression, which may range from moderate sleepiness to an almost coma-like, stuporous condition. The traditional appearance of an isolated benzodiazepine overdose or acute toxicity is characterized by CNS depression accompanied by normal vital signs and vital signs. In the case of pure benzodiazepine toxicity, cardiac-related consequences and deaths are very unusual occurrences. Although less prevalent as compared to barbiturates, respiratory depression or compromise is the most serious side effect that needs prompt treatment. With massive oral ingestions, whether with or without co-ingestants, it is possible to have life-threatening respiratory depression. When benzodiazepines are coupled with other medicines during procedural sedation, especially with opiates such as fentanyl, it is possible to find iatrogenic causes of toxicity in the patient.
The majority of children who suffer from benzodiazepine poisoning will have symptoms within four hours of consumption. When it comes to children, ataxia is the most prevalent symptom of poisoning, appearing in 90 percent of pediatric patients. Respiratory compromise is recorded in fewer than 10% of pediatric cases, and hypotension has not been seen in any of these instances.
Psychomotor slowdown may be particularly severe after the administration of a benzodiazepine for the first time or following a significant dose increase. It may also be seen in individuals, such as the elderly, who have slower rates of metabolism or are more susceptible to central nervous system depression than the general population.
Drowsiness, poor attention, ataxia, dysarthria, motor incoordination, diplopia, muscular weakness, vertigo, and mental confusion are some of the psychomotor symptoms that might occur. The psychomotor effects of benzodiazepines have been studied, and the results indicate that they delay response time and impair driving abilities, increasing the likelihood of motor vehicle accidents in patients who are taking these medications.
A benzodiazepine’s ability to cause anterograde amnesia is what accounts for the positive benefits of benzodiazepines such as midazolam (Versed) when used as a preoperative drug. These particular amnestic effects seem to be distinct from those associated with sedation. In heavy alcohol drinkers who also take benzodiazepines, episodic memory (the recalling of recent events and the conditions in which they happened as well as their time sequences) is notably impaired, and this is more pronounced in those who use both.
Patients who have been using therapeutic dosages of benzodiazepines on a regular basis for more than a year have been shown to have specific deficiencies in visuospatial ability and sustained attention, according to the literature.
Emotional blunting and depression
A link has been shown between the use of benzodiazepines and the development of depressed symptoms, as well as the appearance of suicidal thoughts in certain instances. Certain data suggests that greater benzodiazepine doses are connected with an increased risk of depression and that lowering the dosage or terminating medication may be effective in alleviating depressive symptoms in some patients. 15 It is possible that benzodiazepine-induced depression occurs as a physiologic outcome of a decrease in central monoamine activity, albeit the exact mechanism of action is unknown at this time.
In clinical practice, it is possible to experience “emotional anesthesia.” This impact may be sought after by drug users who have grown more unable to cope with their emotions and other life pressures as time goes on.
Methyldopa adverse effects in pregnancy
Methyldopa was tested on 242 pregnant women who had moderate hypertension at the time of the study (Aldomet). The hypotensive impact of methyldopa in pregnant women was comparable to that seen in non-pregnant adults, and it significantly decreased the incidence of severe hypertension developing during pregnancy and labor. In addition, as the pregnancy progressed, a rising daily dosage of methyldopa was required, and the requirement for extra hypotensive medication was increased.
A total of seventeen (14.5 percent) of the women who were allocated to methyldopa had to be moved to another medicine or had to cease therapy altogether due to mild side effects, the most prevalent of which were lack of energy and dizziness, respectively. There were no negative side effects that were observed. Nine percent of the women who did not get medication had significant hypertension, which necessitated the need for treatment later in their pregnancies. Almost majority of the patients were able to discontinue medication six weeks after giving birth.
Benzodiazepines may cause tolerance to all of their effects, however, this occurs at various speeds and to varying degrees depending on the individual. Because of this quick development of tolerance, hypnotic effects may be used for daytime anxiety reduction, but the long-term treatment of insomnia is more difficult to do successfully. Patients often experience immediate relief from insomnia, followed by a gradual decrease in effectiveness over time.
There is some indication that tolerance to the anxiolytic effect develops more slowly than tolerance to the hypnotic effect, although there is minimal data to suggest that benzodiazepines maintain their effectiveness beyond four to six months of daily usage.
Benzodiazepine medication is often prolonged in order to suppress withdrawal symptoms, which are typically mistaken for anxiety symptoms. Dosage escalation often contributes to the maintenance of the cycle of tolerance and dependency, and patients may have difficulties in stopping medication treatment.
Benzodiazepine medication, depending on the dose, length of therapy, and strength of the drug, might result in psychological and physical dependence in certain patients. Because of this, psychological and physical dependence on a high-potency substance like alprazolam develops more quickly (often within one to two months) than reliance on a long-acting, low-potency medication like chlordiazepoxide, which develops more slowly (typically between three to six months). In the case of physiologic dependency, withdrawal symptoms manifest themselves with a quick dosage decrease or sudden termination of the medication.
Benzodiazepines have been shown to cause psychological dependence on the need for the agent, loss of self-confidence, and varying degrees of drug-seeking behavior or drug abuse in patients who have used them for an extended period of time.
Patients may be hesitant to cease the medication due to misguided anxieties or anticipatory anxiety, which is understandable. Some patients mix alcohol with benzodiazepines when they are unable to get the desired or “required” effects from either medication alone.
Benzodiazepines are seldom the first or only medication of choice when it comes to substance misuse. Benzodiazepine misuse is believed to account for 80 percent of all drug abuse, with opioids being the most prevalent combination. According to the National Institute on Drug Abuse’s two-year treatment outcome study28, 15 percent of heroin users also used benzodiazepines on a daily basis for more than one year, and 73 percent used benzodiazepines more often than once a week for more than one year. According to several studies, anything from 5 percent to as much as 90 percent of methadone users are also habitual users of benzodiazepines on a daily basis. High-dose benzodiazepine addiction is particularly common among patients who are receiving methadone treatment.
According to studies, between 3 and 41% of alcoholics have admitted to abusing benzodiazepines at some point in their lives, most often to reduce the consequences of drunkenness or withdrawal.
The modern alcoholic is often a drug addict who uses a variety of substances. Eighty percent of alcoholics under the age of thirty have been addicted to or use at least one other substance at some point in their lives.
Pharmaceutical companies’ prescriptions are the most common source of supply for persons who misuse benzodiazepines. Prescriptions may also have a market value on the black market, which stimulates rerouting to illegal suppliers. When used in conjunction with other drugs, benzodiazepines can be used to enhance the euphoric effects of opioids (for example, to “boost” methadone doses), to alleviate withdrawal or abstinence syndromes (for example, between heroin “fixes”), to temper cocaine highs, to augment alcohol synergistically, and to modulate withdrawal states.
Because of the fast beginning of action of short-acting benzodiazepines as possible misuse substances, users seem to prefer them over longer-acting benzodiazepines.
The difficulties associated with benzodiazepine dependency, tolerance, withdrawal, rebound, and misuse make them unsuitable for long-term therapy of anxiety disorders in individuals who are also addicted to alcohol or other drugs. An increasing amount of evidence now supports the anxiolytic effects of a wide range of different medications. The use of antidepressants, anticonvulsants, buspirone (Buspar), some antihypertensive medications, and newer neuroleptics has been demonstrated to be beneficial in specific subgroups of people suffering from anxiety disorders.
For patients who are currently struggling with alcohol or drug addiction, as well as those who are recovering from addiction, most addiction medicine professionals consider that benzodiazepines are generally contraindicated. In order to choose an acceptable alternative to a benzodiazepine, clinicians must be able to distinguish between the many subtypes of anxiety disorders that might present in a given patient. Patients should be encouraged to realize that the beginning of action of antidepressants, buspirone, and anticonvulsants is not as quick as that of benzodiazepines and that they should not expect their symptoms to disappear immediately. Therapy may need patience and, due to the possibility of adverse effects, a modest dose may be recommended at first.
What are the long-term effects of benzodiazepines?
Long-term use of benzodiazepines may have a similar effect on the brain as alcohol, and they have been linked to a variety of mental illnesses, including depression, anxiety, post-traumatic stress disorder (PTSD), mania, psychosis, sleep disorders, sexual dysfunction, delirium, and neurocognitive dysfunction.
What is the most common side effect of benzodiazepines used to treat anxiety?
Drowsiness and poor coordination are the most typical adverse effects of benzodiazepine usage, according to the American Psychiatric Association. When benzodiazepines are used in small dosages for a short length of time, such side effects are usually moderate and may not be noticed or bothersome to the patient.
What are the risks of benzodiazepines?
Aside from abuse and dependence, the other major risks of benzodiazepines are cognitive impairment, motor vehicle accidents, and hip fractures in the elderly.
Which benzodiazepine has the least side effects?
Many classic benzodiazepines are broken down in the liver and when taken with medications that prevent this activity, blood levels might increase, resulting in negative effects. Lorazepam, oxazepam and temazepam are less likely to have this risk owing to fewer liver enzyme interactions
- Benzodiazepines: Uses, Side Effects, Interactions & Warnings (drugs.com)
- Benzodiazepines – an overview | ScienceDirect Topics
- Addiction: Part I. Benzodiazepines-Side Effects, Abuse Risk and Alternatives – American Family Physician (aafp.org)
- Benzodiazepines: Uses, Side Effects, Interactions & Warnings (drugs.com)