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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.


Indications

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 (e.g. 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
Alplax® - Argentina
Alpralid® - Israel
Alprax® - India
Alviz® - Indonesia
Alzolam® - India, Malaysia
Apo-Alpraz® - Canada (also made by other companies under different names)
Apraz® - Brazil
Calmax® - Ireland
Constan® - Japan
Frontal XR® - (an extended release formulation) Brazil
Frontal® - Brazil
Frontin® - Hungary, Slovak Republic, Czech Republic
Helex® - Croatia, Slovenia
Kalma® - Australia
Kinax® - Taiwan
Ksalol® - Serbia
Manorest® - Sri Lanka
Misar® - Croatia
Neurol® - Czech Republic, Slovak Republic
Niravam® - (formulation that dissolves on the tongue) United States
Prazolex® - Romania
Ralozam® - Australia
Restyl® - Bahrain, Cyprus, Egypt, India, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Oman, Qatar, Republic of Yemen, Saudi Arabia, Syria, United Arab Emirates
Sedipral® - Paraguay
Solanax® - Japan
Tafil AP® - (an extended release formulation) Mexico
Tafil® - Costa Rica, Denmark, El Salvador, Germany, Guatemala, Honduras, Mexico, Nicaragua, Panama, Venezuela
Trankimazin® - Spain
Tranquinal® - Ecuador, Peru
Xanax XR® - (an extended release formulation) Israel [1], 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
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 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)
Euphoria
Confusion

Less common side effects can include:
Fatigue
Headache

Rare side effects can include:
Sleep apnea
Hypoventilation (Respiratory depression)
Blurred vision
Difficulty in depth perception
Slurred speech or dysarthria
Changes in personality
Confusion
Disorientation
Amnesia (memory impairment)
Vivid dreams and/or nightmares
Jaundice
Tachycardia
Bradycardia
Changes in plasma cortisol and ACTH levels
Blood dyscrasias
Decreased salivation
Increased salivation
Diarrhea
Constipation
Nausea
Elevated hepatic (liver) enzymes
Incontinence

Rare paradoxical side effects can include:
Nervousness
Anxiety
Agitation
Rage
Insomnia
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.

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
Acute intoxication with alcohol, narcotics, or other psychoactive substances
Ataxia
Severe hypoventilation
Acute narrow-angle glaucoma
Severe liver deficiencies (e.g. hepatitis and cirrhosis)
Severe sleep apnea
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
Patients with severe personality disorders
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.


Recreational use

alprazolam 2mg tablets

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.


Legal status

In the United States, alprazolam is a prescription drug and is assigned to Schedule IV of the Controlled Substances Act by the Drug Enforcement Administration. Internationally, alprazolam is included under the United Nations Convention on Psychotropic Substances.