Secondary' depression in panic disorder and agoraphobia. I was an ordinary doctor until I found Medscape. Thus, medical opinion in the U. Usual dosage range IV or IM Pharmacology ; 27 Suppl. Clonazepam Withdrawal Insomnia Can Clonazepam Cause Depression
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Generalized anxiety disorder is probably the commonest of these conditions, followed by panic disorder with or without agoraphobia , and social phobia. Acute stress reactions and anxiety symptoms as part of other psychiatric disorders or physical disorders are very commonly encountered. The benzodiazepines seem to be useful and powerful anxiolytic agents and are generally accepted as such, at least in short-term usage.
Unfortunately, close evaluation of the available data shows even this efficacy to be surprisingly limited. One meta-analysis from Australia examined 81 studies mainly of benzodiazepines in anxiety, as compared to a placebo, and in some studies, to no treatment at all. A large number of short-term trials up to 28 nights attest to the effectiveness of benzodiazepines in the treatment of insomnia.
These effects can be seen both with objective EEG recordings in the sleep laboratory and subjectively with rating scales completed each morning. Although these two sets of data correlate at a notoriously low level, the rating of "a good night's sleep" usually reflects infrequent nocturnal arousals. The effects generally wane beyond 28 nights and even before that time. Whether these unequivocal short-term benefits as anxiolytic and hypnotic agents continue into the long-term remains a subject of controversy.
A further complication is the problem of relapse on discontinuation, which could be interpreted as continued efficacy. This must be distinguished from rebound or withdrawal, evidence that the benzodiazepines were acting merely to suppress discontinuation effects. Thus, the frequent observation that many long-term benzodiazepine users claim continuing benefit cannot be taken at its face value. One important study involved chronically anxious patients who were being treated with benzodiazepines for 6, 14 or 22 weeks.
They were then transferred to placebo for 18, 10 and 2 weeks respectively. Furthermore, in those patients who did not develop withdrawal reactions, the switch to placebo was usually attended by a worsening of anxiety symptoms. The variability between patients is high but these data can be interpreted as showing that long-term use, although probably maintaining some efficacy, also involves an appreciable risk of inducing dependence.
In another study from this group the long-term treatment of chronic anxiety with the benzodiazepine clorazepate was compared with the effects of the non-benzodiazepine, buspirone. All treatments were given for 6 weeks and withdrawn by week By 6 weeks, the initial efficacy of diazepam had waned and by the end of the study period, patients treated with diazepam were actually worse off than those on placebo and the other treatments. The benzodiazepines are used, often at high dose and for months at a time in the management of panic patients.
The panics may be spontaneous PD or occur in agoraphobic situations. The drug promptly suppresses the panics and anxiety and facilitates the application of non-drug measures such as psychotherapy and cognitive behavioural therapy CBT. Efficacy can usually be established in the short-term, although placebo responses can be appreciable. Direct comparisons with other effective anti-panic agents such as imipramine, an SSRI, indicates that such withdrawal after months is often an important problem requiring clinical resources for its management.
Some elucidation of these issues is afforded by study of the long-term efficacy of the hypnotic benzodiazepines because of the availability of objective sleep recordings polysomnogram, PSG. Fairly consistently, sleep EEG measures of hypnotic effect revert to pre-treatment values after weeks. This demonstrates the mis-match between subjective and objective measures. In fact, patients given a benzodiazepine overestimate their sleep duration by an average of 72 minutes as compared with the EEG recordings.
Thus, the symptomatic improvement on an hypnotic and worsening on withdrawal are exaggerated in opposite directions by these subjective discrepancies. To summarise the benefits, benzodiazepine anxiolytic, antipanic and hypnotic effects are certainly useful, indeed, often invaluable in short-term prescription, say up to 2 weeks for hypnotic use, 4 for anxiolytic use, and 12 for antipanic effects. The placebo effects and general measures of support and reassurance are important elements in the responses.
Beyond these watersheds, efficacy wanes but to a variable extent, patient-to-patient, and probably among the individual benzodiazepines. In some patients, tolerance develops with the possibility of rebound or a full withdrawal syndrome on discontinuation. The efficacy of the benzodiazepine as a symptomatic remedy then becomes conflated with its efficacy in suppressing possible withdrawal reactions on discontinuation.
The contribution of these constituents to the apparent therapeutic actions of the benzodiazepine varies from patient-to-patient, and at different phases in the course of treatment. Only by careful clinical questioning and observation can the beneficial elements of benzodiazepine treatment be distinguished from the potential problems of rebound and withdrawal. These will be reviewed under a variety of headings. The psychological effects of the benzodiazepines are divisible into the subjective, behavioural, psychomotor and cognitive.
Subjectively, the benzodiazepines reduce anxiety and induce sleepiness, torpor and relaxation. This is the wanted effect when the medication is taken in a single dose at night to induce sleep but is an unwanted side-effect when administered during the day for generalized or panic anxiety. Sedation occurs in about a third of people given an anxiolytic benzodiazepine, 13 and euphoria may be induced in some.
These effects are most noticeable the first week but wane steadily until the patient can detect no sedation at all. The severity of the sedation depends on dose, individual susceptibility and also on the specific benzodiazepine: Long-acting hypnotics are likely to produce residual sedative effects much into the next day.
Paradoxical effects, although uncommon, can be a major management problem. Abnormal affects may develop such as hostility or depression; antisocial behaviour may supervene with rare cases of violence to persons or property. The interaction with alcohol is particularly hazardous, uncharacteristic acts such as petty theft or sexual improprieties may occur or the patient may break down into uncontrollable weeping. The impulses and acts may perplex the patient who fails to relate them to his medication.
In fact he or she may fear the onset of madness. Reduction in dosage or total discontinuation of the benzodiazepine is usually necessary. Benzodiazepines neither induce nor lessen depression. The euphoriant effects of a benzodiazepine may appear to ameliorate depression. Also, many depressed patients are anxious so that decreasing the anxiety may allow the depressive features greater expression.
Benzodiazepines can impair psychomotor functions such as those involving speed and accuracy. Tasks requiring sustained attention and concentration can be markedly disrupted by administration of a benzodiazepine. Effects are strongly dose-related and also vary from drug to drug. Normal subjects given repeated dosing show the well-known phenomena of tolerance so that impairments wane over a week or so.
The situation in patients is more complex. Anxious or insomniac patients are already impaired in psychological performance because of the effects of the conditions themselves: This improvement swamps any drug-related impairment except when high doses are given. Exceptions to this include the elderly who are typically sensitive to psychomotor-impairing drugs and some tests of very skilled performance where impairments tend to be both detectible and persistent.
Thus, withdrawal from long-term benzodiazepine use may be followed by some improvements. In memory tasks, benzodiazepines disrupt the consolidation process in semantic verbal memory whereby material in short-term stores is transferred to long-term stores. As with psychomotor tests, single-dose studies in normals detect these effects much more reliably than repeated dose studies in patients.
Moreover, tolerance to these effects may be incomplete so that memory difficulties can persist. Memory problems in the elderly taking a benzodiazepine may lead to a mis-diagnosis of dementia. Driving a motor-car is the real-life ability par excellence and impairments are often substantial after a benzodiazepine. Again these are dose-related and particularly noticeable if alcohol is also taken. Epidemiological data indicate that benzodiazepines contribute to road traffic and domestic accidents, although to a much lesser extent than alcohol.
These include vertigo, dizziness, dysarthria and ataxia. In the elderly, incoordination may lead to falls. The progress of child-birth can be impeded by excessive benzodiazepine administration and the baby may be floppy or even undergo a withdrawal reaction. Small amounts of benzodiazepines are secreted in the breast-milk so the mother should not breast feed. Although some drug interactions do occur e. Potentiation of sedative CNS depressants especially alcohol is the main problem.
Overdose is quite frequent but usually the patient recovers within 48 hours. However, benzodiazepines can be dangerous in the young, the old and the physically ill, particularly those with respiratory insufficiency. Tolerance to both the therapeutic and unwanted effects of the benzodiazepines has been mentioned earlier. This uncommonly develops into full-blown tolerance with escalation of dose to several times the therapeutic levels.
Patients on such high doses are physically dependent and may suffer severe withdrawal including fits or a psychotic disorder if the medication is stopped abruptly. These people also show drug-seeking behaviour so they are psychologically dependent as well. This has been most systematically studied following the stopping of hypnotic medication, and is common after high doses of short-acting compounds.
A withdrawal syndrome may ensue after long-term use at therapeutic dosage, even after tapering. They include almost pathognomic perceptual symptoms such as photophobia, hyperacusis and a feeling of incessant movement. The symptoms come on within 48 hours of stopping a medium-acting benzodiazepine such as lorazepam or temazepam, and days of stopping long-acting drugs like diazepam and clorazepate.
The symptoms usually subside over a few weeks but occasional patients complain of persisting problems. Withdrawal from lorazepam is more difficult to accomplish than from diazepam and withdrawal from hypnotics is easier than from those given by day. It is fair to say that the topic of normal-dose dependence remains under debate, 23 but it is generally agreed that it is a relevant factor to consider when starting a patient on a benzodiazepine anxiolytic or hypnotic.
It is difficult to predict who will progress to long-term use and become dependent, and how severe any subsequent withdrawal will be. Less than half of long-term users achieve sustained abstinence, and some become clinically depressed after withdrawal. Finally, the benzodiazepines pose a major addiction problem world-wide. As part of polydrug abuse, benzodiazepines are used to intensify euphoria with opioids, ease the "crash" down from stimulants like amphetamine and cocaine, and provide enough disinhibition to engage in the criminal activities needed to sustain the polydrug habit.
Benzodiazepines are also used by themselves, taken by mouth, sniffed or sometimes intravenously. Injection may be followed by thrombophlebitis and even gangrene. Many other treatments are available, some being appropriate for long-term treatment. For GAD and PD, these alternatives include tricyclic antidepressants TCAs such as imipramine and clomipramine, selective serotonin reuptake inhibitors SSRIs like citalopram, fluoxetine, sertraline, and paroxetine, and monoamine oxidase inhibitors MAOIs both unselective and irreversible like phenelzine, and selective, reversible moclobemide.
Such use of antidepressants is formally approved by the regulatory authorities for panic and phobia indications for some SSRIs. The advantages of antidepressants are definite efficacy and easy withdrawal, and the disadvantages are the various types of side-effect profiles which may compromise compliance. Buspirone, a non-benzodiazepine, acts on serotonin mechanisms and has some efficacy in GAD.
Cautious initial dosage is essential to minimize side-effects such as dizziness; withdrawal is almost always uneventful suggesting little or no dependence potential. Beta-blockers can help patients with performance anxiety with tremor and palpitations. The alternatives for insomnia are, again, the antidepressants, with a preference for sedative agents such as amitriptyline and trazodone.
Nefazodone is believed to have beneficial effects on sleep patterns and may prove to be particularly useful to help manage insomnia associated with depression. Alcohol is a poor hypnotic as it causes rebound insomnia later in the night. A wide range of non-pharmacological treatments are available to aid in the management of anxiety and insomnia.
It is particularly important to appreciate that drug and non-drug treatments can be given in combination as well as in succession. Care is needed with this strategy but evidence is accruing that some forms of such combined therapy produce responses distinctly superior to either treatment alone. How to manage patients with anxiety disorders. An algorithm for the management of the commoner condition, GAD, is set out in figure 1. The plan relates to the primary care context where much of the treatment of this condition takes place.
Physical causes for the anxiety should be excluded at the initial assessment. Thyrotoxicosis is the main differential diagnosis, with phaeochromocytoma a rare one. Caffeine overuse should be enquired for, as should alcohol and substance abuse. An underlying depressive disorder should be sought and excluded. The diagnosis of anxiety disorder is usually easier if the patient presents with psychological rather than physical symptoms.
It is commonly used to treat epilepsy, anxiety disorders, restless legs syndrome, chronic fatigue syndrome, and panic attacks. It is also used to remediate the effects of some antipsychotic medications used with schizophrenia. Users of clonazepam report experiencing drowsiness, impaired cognition, impaired coordination and balance, and dizziness.
Although diazepam is approved to treat anxiety, panic attacks, and insomnia short-term , many of its uses are off-label; including tetanus, mania, alcohol and opiate withdrawal, spastic muscle paresis, and as pre- or post-operative sedation. Frequent side effects include impaired motor function, anterograde amnesia, and depression.
Valium is one of the most well-known drugs of the 20th Century, and the most used prescription drug in the US between and Flunitrazepam is considered to be one of the most addictive benzodiazepines, and its effects are estimated to be times more powerful than diazepam. It is currently considered to be an illegal drug in the United States and is not approved for medical use.
Its use produces many side effects, among them drowsiness, loss of motor control, amnesia, slurred speech, and confusion. Flunitrazepam has an extensive history as a recreational and date-rape drug. It is indicated for the treatment of anxiety disorders, short-term insomnia especially when it is associated with anxiety , acute delirium, several types of epilepsy, and as a pre-medication to decrease the quantity of an anesthetic required before a surgical procedure. It is also used to combat the nausea and vomiting associated with chemotherapy.
Lorazepam is considered to be highly addictive, and is most often used as a short-term treatment. It produces such side effects as blurred vision, drowsiness, dizziness, and orthostatic hypotension a sudden drop in blood pressure when transitioning from lying to sitting or from sitting to standing. Nitrazepam is a strong hypnotic drug, and is most often used to alleviate insomnia short-term. It is sometimes used for the management of seizures.
Initial research indicated that nitrazepam produces significant euphoria, and is likely to become habit-forming if used for extended periods. Common reported side effects are fatigue, drowsiness, loss of coordination, vertigo, dizziness, confusion, and headache. Roche manufactures nitrazepam and it is sold in the U.
Oxazepam is primarily used to treat anxiety and alcohol withdrawal. It is also used to treat insomnia where the individual has difficulty staying asleep. Oxazepam produces many common side effects: Triazolam was briefly removed from several international markets due to concerns regarding the side effects produced with high dosages of the drug. At lower doses, the Food and Drug Administration has declared it safe for use.
It is approved for the treatment of insomnia including jet lag and as a sedative. Triazolam users have described headache, drowsiness, daytime sedation, and lethargy as common reactions. Estazolam is still used for insomnia under the brand name ProSom. It is considered an intermediate half life drug, and peak blood plasma concentration is generally a few hours after the patient swallows the pill. These are prescription drugs for a reason. Use them only under doctor supervision.
For insomnia, the newer Z-drugs are usually prescribed, although doctors may choose a benzodiazepine if there are other illnesses or physiological phenomena involved. Chronic abuse of benzodiazepines and the related change in sleep architecture can lead to an inability to be fully awake during the day. Types of Benzodiazepines Temazepam is a benzodiazepine used primarily as a sleeping pill.