Alprazolam

Alprazolam is a short-acting drug in the benzodiazepine class used to treat anxiety disorders and as an adjunctive treatment for depression.

Alprazolam was invented by Pfizer and is marketed under the trade name Xanax. Its patent expired in September 1993.

Pharmacology

Alprazolam is a triazolobenzodiazepine, that is, a benzodiazepine with a triazolo-ring attached to its structure. Alprazolam binds to the GABAA subtype of the GABA receptor, increasing inhibitory effects of GABA within the central nervous system. The binding site for benzodiazepines is distinct from the binding site for barbiturates and GABA on the GABA receptor.

Unlike other benzodiazepines, alprazolam may also have some antidepressant activity, although clinical evidence of this is lacking.

Pharmacokinetics

The mechanism of action is not fully understood. Alprazolam is readily absorbed from the gastrointestinal tract. The peak plasma concentration is achieved in 1-2 hours. Most of the drug is bound to plasma protein, mainly albumin. Alprazolam is hydroxylated in the liver to α-hydroxyalprazolam, which is also pharmacologically active. This and other metabolites are later excreted in urine as glucuronides. Some of the drug is also excreted in unchanged form.

The main medical uses for alprazolam include:

   

  • Treatment of panic disorder, with or without agoraphobia.

          Alprazolam is very effective in preventing panic attacks. However, despite its efficacy, many psychiatrists are reluctant to use alprazolam for this condition because of the possibility of dependence and interdose ("breakthrough") anxiety due to its short-acting nature. An extended-release formulation of alprazolam known as Xanax XR® was introduced in 2001 and is often preferred.

       

  • Treatment of panic attacks.

          Alprazolam is taken as needed (PRN); 4 to 6 doses per day are the acceptable limit. If dependence seems to develop and/or the limit is exceeded, therapy may be reconsidered and/or discontinued.

        

  • Long-term treatment of severe anxiety disorders.

          Alprazolam may be used for long-term treatment of anxiety if other therapies either do not work or are contraindicated. Duration of therapy in this case is often four months or longer. The decision to use alprazolam for this purpose must be carefully made by a specialized psychiatrist, taking into account the individual's suffering, quality of life, loss of social performance and risk of dependence.

       
  • Adjunctive treatment of depression.

    •       SSRIs (eg. sertraline or fluoxetine) are often co-administered with alprazolam at the outset of long-term SSRI anxiety treatment in order to counteract the initial anxiogenic (anxiety-producing) effects of SSRI treatment. Tricyclic antidepressants and buspirone are also used with alprazolam in refractory (resistant) cases of generalized anxiety disorder.

       

  • Other uses.

          Alprazolam may be used by specialists to treat severe cases of Borderline Personality Disorder. Some studies have shown positive results.

    Availability

    Alprazolam is generally sold in generic form in Italy and the United States. It is also sold under many other brand names, depending on the country:

       

  • Aceprax® - Uruguay

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  • Alplax® - Argentina

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  • Alpralid® - Israel

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  • Alprax® - India

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  • Alviz® - Indonesia

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  • Alzolam® - India, Malaysia

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  • Apo-Alpraz® - Canada (also made by other companies under different names)

       

  • Apraz® - Brazil

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  • Calmax® - Ireland

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  • Constan® - Japan

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  • Frontal XR® - (an extended release formulation) Brazil

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  • Frontal® - Brazil

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  • Frontin® - Hungary, Slovak Republic, Czech Republic

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  • Helex® - Croatia, Slovenia

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  • Kalma® - Australia

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  • Kinax® (景安寧) - Taiwan

       

  • Ksalol® - Serbia

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  • Manorest® - Sri Lanka

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  • Misar® - Croatia

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  • Neurol® - Czech Republic, Slovak Republic

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  • Niravam® - (formulation that dissolves on the tongue) United States

       

  • Paxal® - Iceland

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  • Prazolex® - Romania

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  • Ralozam® - Australia

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  • Restyl® - Bahrain, Cyprus, Egypt, India, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Oman, Qatar, Republic of Yemen, Saudi Arabia, Syria, United Arab Emirates

       

  • Sedipral® - Paraguay

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  • Solanax® - Japan

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  • Tafil AP® - (an extended release formulation) Mexico

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  • Tafil® - Costa Rica, Denmark, El Salvador, Germany, Guatemala, Honduras, Mexico, Nicaragua, Panama, Venezuela

       

  • Trankimazin® - Spain

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  • Tranquinal® - Ecuador, Peru

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  • Xanax XR® - (an extended release formulation) Israel, United States, Portugal

       

  • Xanax® - Australia, Belgium, Croatia, Germany, Greece, Hungary, Ireland, Italy, Netherlands, New Zealand, Pakistan, Portugal, Switzerland, Turkey, United Kingdom, United States

       

  • Xanor® - Austria, Finland, Norway, Philippines, South Africa, Sweden

       

  • Zamhexal® - Australia

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  • Zolarem® - Bahrain, Benin, Burkina-Faso, Cyprus, Egypt, Ethiopia, Gambia, Ghana, Guinea, Iran, Iraq, Israel, Ivory Coast, Jordan, Kenya, Kuwait, Lebanon, Liberia, Libya, Malawi, Mali, Mauritania, Mauritius, Morocco, Niger, Nigeria, Oman, Qatar, Republic of Yemen, Saudi Arabia, Senegal, Seychelles, Sierra-Leone, South Africa, Sudan, Syria, Tanzania, Tunia, Uganda, United Arab Emirates, Zambia, Zimbabwe

       

  • Zoldac® - Benin, Burkina-Faso, Ethiopia, Gambia, Ghana, Guinea, India, Ivory Coast, Kenya, Liberia, Malawi, Mali, Mauritania, Mauritius, Morocco, Niger, Nigeria, Senegal, Seychelles, Sierra-Leone, South Africa, Sudan, Tanzania, Tunia, Uganda, Zambia, Zimbabwe

    Packaging

    Appearance is generally as follows in the United States.

    Alprazolam

    Inscriptions on tablet vary depending on manufacturer.

    .25 mg White oval tablet scored

    .5 mg Peach oval tablet scored (.5 mg and .25 mg Alprazolam may also be found in White round tablet scored)

    1 mg Blue oval scored tablet. May also be called a "football."

    2 mg White rectangle multi-scored tablet. May also be called a "bar."

    Xanax XR®

    .5 mg White pentagonal tablet Imprinted "X /0.5"

    1 mg Yellow square tablet Imprinted "X / 1"

    2 mg Blue round tablet Imprinted "X / 2"

    3 mg Green triangular tablet Imprinted "X / 3"

    Side effects

    Common side effects of alprazolam can include:

       

  • Somnolence (drowsiness)

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  • Euphoria

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  • Confusion

    • Less common side effects can include:

       

  • Fatigue

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  • Headache

    • Rare side effects caninclud

    e:

       

  • Sleep apnoea

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  • Hypoventilation (Respiratory depression)

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  • Blurred vision

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  • Difficulty in depth perception

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  • Slurred speech or dysarthria

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  • Changes in personality

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  • Confusion

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  • Disorientation

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  • Amnesia (memory impairment)

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  • Vivid dreams and/or nightmares

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  • Jaundice

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  • Tachycardia

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  • Bradycardia

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  • Changes in plasma cortisol and ACTH levels

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  • Blood dyscrasias

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  • Decreased salivation

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  • Increased salivation

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  • diarrhoea

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  • Constipation

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  • Nausea

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  • Elevated hepatic (liver) enzymes

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  • Incontinence

    • Rare paradoxical side effects can include:

       

  • Nervousness

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  • Anxiety

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  • Agitation

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  • Rage

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  • Insomnia

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  • Muscle spasms and rigidity

    • Paradoxical side effects are usually a result of too high a dose (sometimes deliberate) and/or combination with alcohol. Adjusting the dosage usually causes them to cease.

    Concentrations of alprazolam in cigarette smokers may be reduced up to 50% when compared to non-smokers.

    Long-term treatment with alprazolam may lead to physical and/or psychological dependence. Users often develop a tolerance to the drug's sedative effects, though tolerance to its anxiolytic efficacy rarely develops when used at theraputic dosage levels.

    There is now a general consensus among many psychiatrists that alprazolam (a so-called 'high-potency' benzodiazepine) poses a particularly high risk for misuse, abuse and dependence. Withdrawal after long-term treatment should be done slowly over a period of weeks (or even months) to avoid serious withdrawal symptoms such as agitation, panic attacks, rebound anxiety, muscle cramps and seizures. Some patients may benefit from a substitution with diazepam or clonazepam as these drugs remain in the bloodstream longer and have a somewhat lower risk of dependency.

    Contraindications

    Use of alprazolam should be avoided in individuals with the following conditions:

       

  • Myasthenia gravis

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  • Acute intoxication with alcohol, narcotics, or other psychoactive substances

       

  • Ataxia

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  • Severe hypoventilation

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  • Acute narrow-angle glaucoma

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  • Severe liver deficiencies (eg. hepatitis and cirrhosis)

       

  • Severe sleep apnoea

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  • Hypersensitivity or allergy to any drug in the benzodiazepine class

    Patients at a High Risk for Abuse and Dependence

    At a particularly high risk for misuse, abuse, and dependence are:

       

  • Patients with a history of alcohol or drug abuse and/or dependence

       

  • Emotionally unstable patients

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  • Patients with severe personality disorders

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  • Patients with chronic pain or other physical disorders

    • Patients from the aforementioned group should be monitored very closely during therapy for signs of abuse and development of dependence. Discontinue therapy if any of these signs are noted. Long-term therapy in these patients is not recommended.

    Alprazolam, like all benzodiazepines, has the potential for abuse, especially in individuals prone to addiction. Although it is not manufactured illegally, it is often diverted to the black market. The state of relaxation, anxiolysis, disinhibition and euphoria induced by benzodiazepines is the main reason for their illicit use.

    Injecting alprazolam is highly dangerous. When crushed in water, it will not dissolve, potentially causing severe damage to arteries. While it is somewhat soluble in alcohol, the combination of the two, particularly when injected, can easily cause a serious (and potentially fatal) overdose. Alprazolam may also be insufflated.

    Alprazolam is sometimes used with other recreational drugs to relieve the panic or distress of dysphoric reactions to psychedelics such as LSD and also to promote sleep in the "come-down" period following use of recreational drugs with stimulant or insomniac properties (such as LSD, cocaine, amphetamines, DXM, and MDMA). It is also often used in conjunction with marijuana or heroin to potentiate the relaxing effect. It is also sometimes used by heroin addicts to suppress withdrawal symptoms.

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