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Alternatives to Benzodiazepines in the Management of Anxiety

This list is long, and most are off-label, although the most prominent medications that treat anxiety disorders are the SSRIs, which are FDA approved and generally effective in managing underlying anxiety disorders. As most type I or late-onset alcoholics suffer from a primary anxiety disorder that often drives their alcohol use, the SSRIs can help them secondarily to moderate their drinking or even help them to achieve abstinence, as discussed in Question 18. Unfortunately, the anxiety that often accompanies alcoholism is quite tenacious and difficult to treat, leading to rather heroic efforts on the part of physicians to try medications off- label. The most common of these most recently has been a class of medications known as atypical antipsychotics. These include most prominently quetiapine (Seroquel), which is discussed further in managing insomnia; however, other atypical antipsychotics have also been tried with varying degrees of success. These other agents include olanzapine (Zyprexa), risperidone (Risperdal), ziprasidone (Geodon), and aripiprazole (Abilify). All of these medications are FDA approved for schizophrenia and bipolar disorder so they are clearly used off-label when prescribed for anxiety. And their use comes with a price. First, weight gain can be an issue. Second, metabolic changes can also occur, including increased blood sugar, cholesterol, and triglycerides. Finally, in older people, there is a small increase in the risk of having cerbrovascular accidents. Despite these drawbacks, they can be safe and effective agents in their own right, and their use should be considered when the anxiety is severely debilitating and not responding to more traditional regimens. Anticonvulsant medications are used off-label to treat anxiety. These include valproic acid (Depakote), gabapentin (Neurontin), carbamazepine (Tegretol), and the newer anticonvulsants lamotrigine (Lamictal), tiagabine (Gabatril), and pregabalin (Lyrica). Table 14, which also includes medications from Question 56, contains a general list of some of the medications used in the treatment of anxiety and insomnia.

Table 14 Medications for Anxiety/lnsomnia

Medication

Class

FDA-Approved Use

Off-label Use

Major Drawback

Zolpidem, et al.

Non-BZDP hypnotic

Short term treatment for insomnia

Chronic insomnia

Rebound and chronic

insomnia

Lorazépam, et al.

BZDP

Short term treatment for anxiety, seizures

Chronic anxiety

Dependency, tolerance, and withdrawal

Fluoxetine, et al.

SSRI

Depression, anxiety

OCD, premature ejaculation

Sexual dysfunction

Trazadone

Atypical Antidepressant

Depression

Anxiety, insomnia

Low blood pressure, hangover

Ramelteon

Melatonin Receptor Agonist

Insomnia

None

Nonsedating

Mirtazepine

Atypical Antidepressant

Depression

Anxiety, insomnia

Dry mouth, constipation

Doxepine

Tricyclic Antidepressant

Depression

Insomnia, anxiety, panic, neuropathic pain

Dry mouth, constipation, weight gain

Quetiapine

Atypical Antipsychotic

Schizophrenia, bipolar disorder

Impulsivity, anger management, anxiety, insomnia

Weight gain, metabolic effects

Olanzapine

Atypical Antipsychotic

Schizophrenia, bipolar disorder

Impulsivity, anger management, anxiety, insomnia

Weight gain, metabolic effects

Risperidone

Atypical Antipsychotic

Schizophrenia, bipolar disorder

Impulsivity, anger management, anxiety, insomnia

Weight gain, metabolic effects, increased prolactin, extra pyramidical side effects*

""Include muscle spasms, tremors, restlessness, and other abnormal movements.

(continued)

Medication

Class

FDA-Approved Use

Off-label Use

Major Drawback 1

Ziprasidone

Atypical Antipsychotic

Schizophrenia, bipolar disorder

Impulsivity, anger management, anxiety

Weight gain and metabolic effects less, less sedating

Aripiprazole

Atypical Antipsychotic

Schizophrenia, bipolar disorder

Impulsivity, anger management

Weight gain and metabolic effects less, less sedating

Carbarn azepine

Anticonvulsant

Seizures, neuropathic pain

Bipolar disorder, depression

Toxic in overdose, blood levels required

Tiagabine

Anticonvulsant

Seizures

Anxiety, mania

Delirium

Valproate

Anticonvulsant

Seizures, bipolar disorder, neuropathic pain

Anxiety, panic

Weight gain, birth defects

Gabapentin

Anticonvulsant

Seizures, neuropathic pain

Anxiety, insomnia, restless legs

Generally of limited effectiveness

Lamotrigine

Anticonvulsant

Seizures, bipolar depression

Unipolar depression, anxiety

Dangerous rash if increased too rapidly

Pregabalin

Anticonvulsant

Seizures, neuropathic pain

Insomnia, anxiety

Delirium

Diphenhydramine

Over-the-counter allergy medication

Allergies, sleep

None

Weight gain, hangover, dry mouth

Distinguishing Discontinuation Syndromes

Many of these medications, including the SSRIs, the atypical antipsychotics, and some of the anticonvulsants, cannot be discontinued abruptly or else various side effects can occur. The side effects are known collectively as discontinuation syndromes. It is important to distinguish between four types of discontinuation syndromes that can occur when you stop a medication that you have been taking daily for an extended period of time. These four syndromes include withdrawal (which we have previously discussed), rebound, recurrence, and medication specific. Withdrawal is accompanied by clear physiologically measurable changes, including vital signs changes, skin color and temperature changes, and psychological distress. For some drugs, such as benzodiazepines, this can be a life- threatening emergency. For this reason, one needs to always consult a physician when deciding to discontinue a medication to see whether such a withdrawal syndrome could occur. Rebound occurs when the symptoms for which one was receiving the medication become transiently worse than the symptoms one had before treatment commenced. This is a potential risk for any sleep medication from which rebound insomnia can be very severe; however, this is a transient effect that abates within days. Unfortunately, most people don't realize that rebound is expected and transient and immediately they go back on their sleeping medications. Physiological changes generally do not accompany rebound. Recurrence is simply the return of symptoms for which one originally received the medication. Recurrence is more delayed in the time line after stopping a medication than either withdrawal or rebound. Finally, medication-specific discontinuation syndromes occur with respect to the SSRIs. Symptoms can start abruptly and last for days to weeks depending on the medication one stopped. The symptoms include headaches, dizziness, electrical sensations running down the arms and legs, and feeling like you are coming down with the flu. Often the symptoms are misinterpreted as a recurrence of depression. Typically, if one begins to experience symptoms as early as a few days after stopping antidepressant medications, these actually represent rebound or a discontinuation syndrome (no measurable physiological changes). Rarely is it due to recurrence. Thus, it is a good idea to taper the medications. When the medications are appropriately tapered, any symptoms that return can properly be attributed to recurrence, and thus, increasing the medication back to a therapeutic dose may be a wise choice. In summary, although these medications can cause various discontinuation syndromes, they are not addictive.

 
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