An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes (2005) people with a depressive illness will experience a therapeutic effect to their mood; however, this will not be experienced in healthy individuals. Drugs including the monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs) are most commonly associated with the term. These medications are among those most commonly prescribed by psychiatrists and other physicians, and their effectiveness and adverse effects are the subject of many studies and competing claims. Many drugs produce an antidepressant effect, but restrictions on their use have caused controversy and off-label prescription is a risk, despite claims of superior efficacy.

Opioids were used to treat major depression until the late 1950s. Amphetamines were used until the mid 1960s. Prescribing opioids or amphetamines for depression falls into a legal grey area. Research has only rarely been conducted into the therapeutic potential of opioid derivatives for depression in the past sixty years, whereas amphetamines have found a thriving market for conditions as widely arrayed as attention deficit disorder, narcolepsy, and obesity, and continue to be studied for myriad applications. Both opioids and amphetamines induce a therapeutic response very quickly, showing results within twenty-four to forty-eight hours; the therapeutic ratios for both opioids and amphetamines are greater than those of the tricyclic anti-depressants. In some of this little, heavily restricted research, the opioid buprenorphine has shown the greatest potential for treating severe, treatment-resistant depression of any known pharmaceutical in a small study that is generally recognized and was published in 1995, but has never been pursued due to the social stigma attached to opioids in addition to that attached to mental illness in America.

Most typical antidepressants have a delayed onset of action (2–6 weeks) and are usually administered for anywhere from months to years. Despite the name, antidepressants are often used controversially, and with a dearth of empirical evidence to support their indication, off-label to treat other conditions, such as anxiety disorders, obsessive compulsive disorder, eating disorders, chronic pain, and some hormone-mediated disorders such as dysmenorrhea. Alone or together with anticonvulsants (e.g., Tegretol or Depakote), these medications can be used to treat attention-deficit hyperactivity disorder (ADHD) and substance abuse by addressing underlying depression. Also, antidepressants have been used sometimes to treat snoring and migraines.

Other medications that are not usually called antidepressants, including antipsychotics in low doses and benzodiazepines,  may be used to manage depression, although benzodiazepines cause a physical dependence to form. Stopping benzodiazepine treatment abruptly can cause unpleasant withdrawal symptoms. An extract of the herb St John’s Wort is commonly used as an antidepressant, although it is labeled as a dietary supplement in some countries. The term antidepressant is sometimes applied to any therapy (e.g., psychotherapy, electro-convulsive therapy, acupuncture) or process (e.g., sleep disruption, increased light levels, regular exercise) found to improve a clinically depressed mood.

Inert placebos can have significant antidepressant effects, and so to establish a substance as an “antidepressant” in a clinical trial it is necessary to show superior efficacy to placebo. A review of both published and unpublished trials submitted to the U.S. Food and Drug Administration (FDA) found that the published trials had a 94% success in treating depression while the unpublished literature had below 50% success. Combined, all studies showed 51% efficacy – only two points better than that of placebo. The difference in effect between active placebos and several anti-depressants appeared small and strongly affected by publication bias. There is some evidence to suggest that mirtazapine and venlafaxine may have greater efficacy than other antidepressants in the treatment of severe depression.

Source: http://en.wikipedia.org/wiki/Antidepressant

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Generic and Trade Names of Medications (Trade Names Are Capitalized) Use of Medication

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Lustral tablets contain the active ingredient sertraline hydrochloride, which is a type of antidepressant known as a selective serotonin reuptake inhibitor (SSRI). (NB. Sertraline tablets are also available without a brand name, ie as the generic medicine.)

Antidepressant medicines act on nerve cells in the brain. In the brain there are numerous different chemical compounds called neurotransmitters. These act as chemical messengers between the nerve cells. Serotonin is one such neurotransmitter and has various functions that we know of.

When serotonin is released from nerve cells in the brain it acts to lighten mood. When it is reabsorbed into the nerve cells, it no longer has an effect on mood. It is thought that when depression occurs, there may be a decreased amount of serotonin released from nerve cells in the brain.

SSRIs work by preventing serotonin from being reabsorbed back into the nerve cells in the brain. This helps prolong the mood lightening effect of any released serotonin. In this way, sertraline helps relieve depression.

Sertraline may also be used in the treatment of obsessive compulsive disorder and post-traumatic stress disorder. It is not fully understood how it works in these conditions.

It may take between two to four weeks for the benefits of this medicine to appear, so it is very important that you keep taking it, even if it doesn’t seem to make much difference at first. If you feel your depression has got worse, or if you have any distressing thoughts or feelings in these first few weeks, then you should talk to your doctor.
What is it used for?
Depression in adults
A psychiatric disorder in which tasks are excessively repeated (obsessive-compulsive disorder) in adults and children aged six years and over
Post-traumatic stress disorder in adult women
Warning!
Depression and other pschiatric illnesses are associated with an increased risk of suicidal thoughts, self-harm, and suicide. You should be aware that this medicine may not start to make you feel better for at least two to four weeks. However, it is important that you keep taking it in order for it to work properly and for you to feel better. If you feel your depression or anxiety has got worse, or if you have any distressing thoughts, or feelings about suicide or harming yourself in these first few weeks, or indeed at any point during treatment or after stopping treatment, then it is very important to talk to your doctor.
This medicine may reduce your ability to drive or operate machinery safely. Do not drive or operate machinery until you know how this medicine affects you and you are sure it won’t affect your performance.
It is recommended that you avoid drinking alcohol while taking this medicine.
SSRI antidepressants have been associated with the development of unpleasant or distressing restlessness and the need to move, often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. If you experience these symptoms you should consult your doctor.
Antidepressants may cause the amount of sodium in the blood to drop – a condition called hyponatraemia. This can cause symptoms such as drowsiness, confusion, muscle twitching or convulsions. Elderly people may be particularly susceptible to this effect. You should consult your doctor if you develop any of these symptoms while taking this medicine, so that your blood sodium level can be checked if necessary.
If you experience seizures (convulsions or fits) while taking this medicine, consult your doctor immediately, as you will need to stop treatment with this medicine. This also applies if you suffer from epilepsy and experience more seizures than normal after starting this medicine.
You should not suddenly stop taking this medicine, as this can cause withdrawal symptoms such as dizziness, sleep disturbances (including intense dreams), nausea, headache, a feeling of weakness, pins and needles and anxiety. Withdrawal symptoms are temporary and are not due to addiction or dependence on the medicine. They can usually be avoided by stopping the medicine gradually, usually over a period of weeks or months, depending on your individual situation. Follow the instructions given by your doctor when it is time to stop treatment with this medicine. On very rare occasions some people have experienced withdrawal symptoms after accidentally missing a dose of this medicine.
Following a review of the safety and efficacy of SSRIs to treat depression in children under 18 years of age (unlicensed use), the Committee on Safety of Medicines (CSM) has concluded that the risks of sertraline outweigh the benefits for treating depressive illness in this age group. If you are under 18 and taking sertraline for depression you should consult your doctor for advice, but do not suddenly stop taking it as this can cause withdrawal symptoms. Sertraline may be used for obsessive-compulsive disorder in children aged six years and over, but is not recommended for younger children.
Use with caution in
Elderly people
Young adults
History of suicidal behaviour or thoughts
History of mania or hypomania
People also receiving electroconvulsive therapy (ECT)
Decreased kidney function
Decreased liver function
Diabetes
Epilepsy
History of bleeding disorders
People taking medicine that affects blood clotting (eg anticoagulants such as warfarin)
Not to be used in
Children and adolescents under 18 years of age for the treatment of depressive illness
People who have taken a monoamine-oxidase inhibitor antidepressant (MAOI) in the last 14 days
Manic episodes of manic depression (bipolar affective disorder)
Severely decreased liver function
Uncontrolled epilepsy
People taking the antipsychotic medicine pimozide

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.
Pregnancy and Breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.
The safety of this medicine in pregnancy has not been established. It should therefore be used with caution during pregnancy, and only if the benefits to the mother outweigh any risks to the foetus. Seek medical advice from your doctor.
This medicine passes into breast milk, however the effect of this on the nursing infant is unknown. For this reason women who need to take this medicine should consider not breastfeeding. Seek medical advice from your doctor.
Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.
Disturbances of the gut such as nausea, vomiting, diarrhoea or abdominal pain
Indigestion (dyspepsia)
Loss of appetite
Shaking, usually of the hands (tremor)
Dizziness
Difficulty in sleeping (insomnia)
Sleepiness (somnolence)
Increased sweating
Dry mouth
Sexual problems
Headache
Anxiety and agitation
Pins and needles (paraesthesia)
Changes in blood pressure
Seizures
Loss of memory (amnesia)
Liver disorders

The side effects listed above may not include all of the side effects reported by the drug’s manufacturer.

For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.
How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while taking this one, to ensure that the combination is safe.

Sertraline should not be taken at the same time as monoamine oxidase inhibitor medicines (MAOIs). These include monoamine oxidase inhibitor antidepressants such as phenelzine, tranylcypromine and moclobemide, the antibiotic linezolid and the anti-Parkinson’s medicine selegiline. Sertraline should not be started until at least at least a day after stopping moclobemide or linezolid, and at least two weeks after stopping other monoamine oxidase inhibitors. Similarly, treatment with any MAOIs should not be started until at least two weeks after stopping treatment with sertraline.

Sertraline must not be taken with the antipsychotic medicine pimozide.

Sertraline should not be taken in combination with benzodiazepines or other tranquilisers by people who need to drive or operate machinary.

There may be an increased risk of side effects if sertraline is taken with the following medicines, which also enhance the activity of serotonin in the brain:
lithium
triptans for migraine, eg sumatriptan
tramadol
tryptophan.

The herbal remedy St John’s wort should not be taken with sertraline for the same reason.

Sertraline may increase the blood levels of the following medicines:
clozapine
some tricyclic antidepressants (imipramine, desipramine, nortriptyline and possibly amitriptyline).

Sertraline may increase the effect of anti-blood-clotting medicines (anticoagulants) such as warfarin, and this may increase the risk of bleeding. If you are taking an anticoagulant with this medicine, your blood clotting time should be regularly monitored.

As SSRIs have been associated with bleeding abnormalities, the following medicines, which are known to affect the ability of the blood to clot, should be used with caution with sertraline:
tricyclic antidepressants
some antipsychotic medicines
some antisickness medicines, eg prochlorperazine
aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen
ticlopidine
dipyridamole.

Treatment with this medicine may alter control of blood sugar in people with diabetes, who may need an adjustment in their dose of insulin or antidiabetic tablets. People with diabetes should discuss this with their doctor.

Sertraline blood levels may be increased by cimetidine and this may increase the risk of sertraline side effects.
Other medicines containing the same active ingredient

Sertraline tablets are available without a brand name, ie as the generic medicine.

Source: http://www.netdoctor.co.uk/medicines/100001555.html

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Antidepressant drugs are medicines that relieve symptoms of depressive disorders.

Purpose

Depressive disorders may either be unipolar (depression alone) or bipolar (depression alternating with periods of extreme excitation). The formal diagnosis requires a cluster of symptoms, lasting at least two weeks.

These symptoms include, but are not limited to, mood changes, insomnia or hypersomnia, and diminished interest in daily activities.

The symptoms are not caused by any medical condition, drug side effect, or adverse life event. The condition is severe enough to cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Secondary depression, or depression caused by unfavorable life events, is normally self limiting, and may best be treated with cognitive/behavioral therapy rather than drugs.

Description

Antidepressant agents act by increasing the levels of excitatory neurostransmitters, or nerve cell chemicals that act as messengers in the brain’s nervous system. In 2003, a report showed that in addition to treating depression, use of antidepressant drugs may protect the brain from damage depressive episodes cause to the hippocampus, the area of the brain involved in learning and memory. Antidepressant drugs may be prescribed as a first-line treatment for depression, or in conjunction with other methods of controlling depression, such as behavioral therapy and exercise.

The main types of antidepressant drugs in use today are listed below, though the drugs available change frequently. For example, in mid-2003, the manufacturer of Wellbutrin released Wellbutrin XL, the only once-daily norepinephrine and dopamine reuptake inhibitor for treating depression in adults.

tricyclic antidepressants, such as amitriptyline (Elavil), imipramine (Tofranil), nortriptyline (Pamelor)

selective serotonin reuptake inhibitors (SSRIs or serotonin boosters), such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft)

monoamine oxidase inhibitors (MAO inhibitors), such as phenelzine (Nardil), and tranylcypromine (Parnate)

tetracyclic compounds and atypical antidepressants which do not fall into any of the above categories

Selective serotonin reuptake inhibitors maintain levels of the excitatory neurohormone serotonin in the brain. They do not alter levels of norepinephrine. These have become the drugs of choice for a variety of psychiatric disorders, primarily because of their low incidence of severe side effects as compared with other drugs in this therapeutic class. SSRIs show similar actions and side effect profiles, but may vary in duration of action.

Tricyclic compounds, identified by their chemical structure containing three carbon rings, are an older class of antidepressants. Although generally effective, they have a high incidence of anticholinergic effects, notably dry mouth and dry eyes, which can cause discomfort. They also cause cardiac arrythmias. Because tricyclics act on both serotonin and norepinephrine, they may have some value in treatment of patients who fail to respond to SSRIs. Drugs in this class often are available at low prices, which may be significant when cost is a major factor in treatment. They also have been found useful in control of some neurologic pain syndromes.

Tricyclic antidepressants are similar, but may vary in severity of side effects, most notably the degree of sedation and the extent of the anticholinergic effects.

Tetracyclic compounds and atypical antidepressants are chemically distinct from both the major groups and each other. Although maprotilene (no brand name, marketed in generic form only) and mirtazepine (Remeron) are similar in chemical structures, they differ in their balance of activity on serotonine and norepinephrine levels.

Monoamine oxidase inhibitors (phenelzine [Nardil], tranylcypromine [Parnate]) have largely been supplanted in therapy because of their high risk of severe adverse effects, most notably severe hypertension. They act by inhibiting the enzyme monoamine oxidase, which is responsible for the metabolism of the stimulatory neurohormones norepinephrine, epinephrine, dopamine, and serotonin. The MAOIs are normally reserved for patients who are resistant to safer drugs. Two drugs, eldepryl (Carbex, used in treatment of Parkinson’s disease) and the herb, St. John’s wort, have some action against monoamine oxidase B, and have shown some value as anti-depressants. They do not share the same risks as the non-selective MAO inhibitors.

All antidepressant agents, regardless of their structure, have a slow onset of action, typically three to five weeks. Although adverse effects may be seen as early as the first dose, significant therapeutic improvement is always delayed. Similarly, the effects of antidepressants will continue for a similar length of time after the drugs have been discontinued.

Recommended dosage

Dose varies with the specific drug and patient. Specialized references or a physician should be consulted.

Precautions

Antidepressants have many significant cautions and adverse effects. Although a few are listed here, specific references should be consulted for more complete information.

SSRIs. The most common side effect of SSRIs is excitation and insomnia. Excitation has been reported in over 20% of patients, and insomnia in 33%. Significant weight loss has been frequently reported, but most commonly in patients who are already underweight. A 2003 report showed that SSRIs also increase the risk of upper gastrointestinal tract bleeding. SSRIs may cause some sedation, and patients should be cautioned not to perform tasks requiring alertness until they have evaluated the effects of these drugs. SSRIs are pregnancy category C drugs. In 2003, a new report demonstrated that late-term (third trimester) use of these drugs could cause neurological symptoms in newborns, including tremor, restlessness and rigidity. Most SSRIs are excreted in breast milk, and there have been anecdotal reports of drowsiness in infants whose mothers were taking SSRIs while breastfeeding.

Most notably, a joint panel of the U.S. Food and Drug Administration (FDA) issued strong warnings to parents and physicians in 2004 about the risk of suicidal behavior in children and adolescents taking SSRIs.

Tricyclic antidepressants. Amoxepine (not marketed by brand, generic available), although a tricyclic antidepressant rather than a neuroleptic (major tranquilizer), displays some of the more serious effects of the neuroleptics, including tardive dyskinesias (drug induced involuntary movements) and neuroleptic malignant syndrome, a potentially fatal syndrome with symptoms including high fever, altered mental status, irregular pulse or blood pressure, and changes in heart rate. These adverse effects have not been reported with other tricyclic antidepressants.

The most common adverse effects of tricyclic antidepressants are sedation and the anticholinergic effects, such as dry mouth, dry eyes, and difficult urination. Alterations in heartbeat also are common, and may progress to congestive heart failure, stroke, and sudden death.

Tricyclic antidepressants are in pregnancy categories C or D, although there have been no formal studies of the drugs on fetal development. There are no studies of effects on newborns, but some anecdotal reports of malformations have resulted from animal studies. The drugs are excreted in breast milk.

Monoamine oxidase inhibitors. The greatest risk associated with these drugs is a hypertensive crisis which may be fatal and most often occurs when the drugs are taken with interacting foods or drugs. More common adverse reactions may include low blood pressure and slowing of heartbeat. Sedation and gastrointestinal disturbances also are common. MAOIs are in pregnancy category C. Safety in breast feeding has not been established.

Tetracyclics and atypicals. Because these drugs are individual, there are no group patterns of adverse reactions. Specific references should be consulted.

Interactions

The antidepressants have many drug interactions, some severe. Although a few are listed here, specific references should be consulted for more complete information.

SSRIs should not be administered with MAOIs. A wash-out period of about four weeks should be allowed before switching from one class of drugs to the other, five weeks if switching from fluoxetine (Prozac) to an MAOI.

MAOIs have many interactions, however the best known are those with foods containing the amino acid tyramine. These include aged cheese, chianti wine, and many others. Patients and providers should review the MAOI diet restrictions before using or prescribing these drugs. Because of the severity of MAOI interactions, all additions to the patient’s drug regimen should be reviewed with care.

Tricyclic compounds have many interactions, and specialized references should be consulted. Specifically, it is best to avoid other drugs with anticholinergic effects. Tricyclics should not be taken with the antibiotics grepafloxacin and sprafloxacin, since the combination may cause serious heart arrythmias.

Tricyclic compounds should not be taken with the gastric acid inhibitor cimetidine (Tagamet), since this increases the blood levels of the tricyclic compound. Other acid inhibiting drugs do not share this interaction.

SSRIs interact with a number of other drugs that act on the central nervous system. Care should be used in combining these drugs with major or minor tranquilizers, or with anti-epileptic agents such as phenytoin (Dilantin) or carbamazepine (Tegretol). In 2003, one of the biggest concerns regarding new prescriptions for tricyclic antidepressants was data concerning overdoses from these drugs. Information in Great Britain showed that this class of antidepressants was responsible for more than 90% of all deaths from antidepressant overdose. Physicians were being advised to prescribe SSRIs in new patients, but not to change the course of those who had taken tricyclics for years with success.

Key Terms

Cognitive behavioral therapy
A type of psychotherapy in which people learn to recognize and change negative and self-defeating patterns of thinking and behavior.

Depression
A mental condition in which people feel extremely sad and lose interest in life. People with depression also may have sleep problems and loss of appetite and may have trouble concentrating and carrying out everyday activities.

Pregnancy category
A system of classifying drugs according to their established risks for use during pregnancy. Category A: Controlled human studies have demonstrated no fetal risk. Category B: Animal studies indicate no fetal risk, but no human studies; or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate human or animal studies; or adverse fetal effects in animal studies, but no available human data. Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks outweigh any benefits.

For Your Information

Resources

Periodicals

“Antidepressant Drugs May Protect Brain from Damage.” Mental Health Weekly Digest (August 18, 2003): 2.

“FDA Approves Once-daily Supplement.” Biotech Week (September 24, 2003): 6.

“FDA Panel Urges Stronger Warnings of Child Suicide.” SCRIP World Pharmaceutical News (February 6, 2004): 24.

“GPs Told Not to Prescribe Tricyclics.” Pulse (October 13, 2003): 1.

“Late-term Exposure to SSRIs May Cause Neurological Symptoms in Babies.” Drug Week (August 8, 2003): 255.

“SSRIs Increase the Risk of Upper GI Bleeding.” Psychiatric Times (July 1, 2003): 75.

Gale Encyclopedia of Medicine, Published December, 2002 by the Gale Group The Essay Author is Samuel D. Uretsky, PharmD.
Source: http://www.healthatoz.com/healthatoz/Atoz/common/standard/transform.jsp?requestURI=/healthatoz/Atoz/ency/antidepressant_drugs.jsp

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