Tuesday 26 May 2015

What are antidepressants,How do antidepressant medicines work?



Antidepressants are psychiatric medications given to patients with depressive disorders to alleviate symptoms. They correct chemical imbalances of neurotransmitters in the brain which probably cause changes in mood and behavior. Antidepressants may be used for a wide range of psychiatric conditions, including social anxiety disorder, anxiety disorders,
and dysthymia (mild chronic depression).
Antidepressants were initially developed in the 1950s. Their use has become progressively more common over the last twenty years.

Antidepressant usage increasing

In 1996 there were 13.3 million people using antidepressants in the United States. By 2010, the figure stood at 23.3 million people. Researchers from Columbia University Medical Center, the New York State Psychiatric Institute, and the University of Pennsylvania added that rates remained low among racial and ethnic minorities.
They believe antidepressant usage has become more common because:
  • There has been a broadening in the concepts of need for mental health treatment
  • Campaigns to promote mental health care have become more widespread
  • Mental health treatments have become more widely accepted by the public
The Centers for Disease Control and Prevention1 (CDC) reported that antidepressant usage in the USA among people aged 12 or more years rose by 400% between 1988-1994 and 2005-2008.
According to data gathered from public health authorities in Canada, Western Europe and Australasia, increased antidepressant usage has been a progressively common trend in most industrialized countries.

How do antidepressants work?

This YouTube video by Psychiatric Science explains how antidepressants work.

There are many types of antidepressants

According to the Royal College of Psychiatrists2, England, there are nearly thirty different kinds of antidepressants, which can be divided into five main types:
  • Monoamine oxidase inhibitors (MAOIs) - also known as monoamine oxidase inhibitors, are a kind of antidepressant that inhibit the action of monoamine oxidase, a brain enzyme. Monoamine oxidase helps break down neurotransmitters, such as serotonin.

    If less serotonin is broken down, the patient hopefully has more stabilized moods and less anxiety. Doctors usually use MAOIs if SSRIs have not worked, because MAOIs clash with a considerable number of other medications and some foods.

    MAOIs have the following possible side effects: blurred vision, rash, seizures, edema, weight loss, weight gain, sexual dysfunction, diarrhea, nausea, constipation, anxiety, insomnia, drowsiness, headache, dizziness, arrhythmia, fainting, feeling faint when standing up (postural hypotension), and hypertension.

    Examples of Monoamine Oxidase Inhibitors are: phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan) and selegiline (EMSAM, Eldepryl).

  • Noradrenaline and Specific Serotoninergic Antidepressants (NASSAs) - a class of compounds which are used in the treatment of anxiety disorders, some personality disorders, and depression.

    NASSAs have the following possible side effects: constipation, dry mouth, weight gain, drowsiness, sedation, blurred vision and dizziness. More serious adverse reactions include: seizures, white blood cell reduction, fainting, and allergic reactions.

    Examples of Noradrenaline and Specific Serotoninergic Antidepressants include: Mianserin (Tolvon) and Mirtazapine (Remeron, Avanza, Zispin)

  • Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs) - a class of drugs used to treat major depression, mood disorders, and possibly but less commonly ADHD (attention deficit hyperactivity disorder), obsessive compulsive disorder, anxiety disorders, menopausal symptoms, fibromyalgia, and chronic neuropathic pain.

    SNRIs raise levels of serotonin and norepinephrine, two neurotransmitters in the brain - they both play a key role in stabilizing mood. (See below in side effects for SSRIs, which are very similar)

    Examples of Serotonin Norepinephrine Reuptake Inhibitors are: duloxetine (Cymbalta), venlafaxine (Effexor) and desvenlafaxine (Pristiq). Desvenlafaxine was found to be especially helpful in alleviating the symptoms of major depression in menopausal or pre-menopausal women, according to a study carried out by a team at Virginia Commonwealth University.

    • Photo of Prozac box
    Prozac (fluoxetine) is probably the most widely known antidepressant worldwide among lay people.
  • Selective Serotonin Reuptake Inhibitors (SSRIs)- these are the most commonly prescribed antidepressants. Experts say that SSRIs are not only very effective in treating depression; they also have fewer side-effects than the other types.

    SSRIs block the reuptake (absorption) of serotonin in the brain, thus helping the brain cells receive and send messages, which results in better and more stable moods. They are called "selective" because they seem to mainly affect serotonin, and not the other neurotransmitters.

    SSRIs and SNRIs may have the following side effects: hypoglycemia, low sodium, nausea, rash, dry mouth, constipation, diarrhea, weight loss, sweating, tremor, sedation, sexual dysfunction, insomnia, headache, dizziness, anxiety, agitation, and abnormal thinking.

    Examples of SSRI antidepressants are: citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil) and sertraline (Zoloft)

  • Tricyclics - they are called "tricyclics" because there are three rings in the chemical structure of these medications. This class of medication is used to treat depression, and also some types of anxiety, fibromyalgia, and to control chronic pain.

    Tricyclics may have the following side effects: seizures, insomnia, anxiety, arrhythmia, hypertension, rash, nausea, vomiting, abdominal cramps, weight loss, constipation, urinary retention, increased pressure on the eye, and sexual dysfunction.

    Examples of tricyclic antidepressants are: amitriptyline (Elavil), amoxapine- clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil) and trimipramine (Surmontil)
Antidepressants are not all the same, how they affect neurotransmitters, how they are used, and what adverse effects or drug interactions are associated with them differ. One patient may not respond to one type of antidepressant and do better with another, while another person with a similar condition might respond the other way round.
Antidepressants and cardiovascular disease risk - researchers from the Emory University School of Medicine, who carried out a study of twin veterans, found that antidepressant usage is associated with developing thicker arteries, which may contribute to a higher heart disease and stroke risk.

Most antidepressants take a while to work

Most antidepressants take a few weeks to work. They are usually taken for a few months or several years.
Lack of compliance is a serious problem in getting the best out of antidepressants. Compliance means sticking to the treatment regime, taking the tablets at the same time every day, not forgetting to take them, etc. Patients with depression may not like having to wait several weeks for a result, and many drop out before the medication has had a chance to work.

Antidepressants are used to treat several conditions and illnesses

Despite the name - antidepressants - these medications can be used to treat several different types of illnesses and conditions, and not all of them psychiatric ones.
Primary (approved) uses of antidepressants are for the treatments of:
  • Agitation
  • Obsessive compulsive disorders (OCD)
  • Childhood enuresis (bedwetting)
  • Depression
  • Generalized anxiety disorder
  • Major depressive disorder
  • Manic-depressive disorders
  • Posttraumatic stress disorder (PTSD)
  • Social anxiety disorder
Some "off-label" uses of antidepressant (for an unapproved indication) include:
Antidepressants were ineffective for treating repetitive behaviors in children with autism, researchers from Yale University School of Nursing and the Child Study Center, found.

How effective are antidepressants?

According to the Royal College of Psychiatrists2, the percentage of people who reported a significant improvement after three taking an antidepressant for three months were:
  • 50% to 60% of those taking an antidepressant
  • 25% to 30% of those given a placebo (dummy drug)
For a medication to be assessed properly there has to be a clinical trial, preferably a double-blind one, comparing the drug with either another one or a placebo. "Double-blind" means that neither the doctor nor the patient knows who is having the drug and who is having the placebo.
Placebos do have an effect on improving symptoms in many illnesses and conditions; we call this the "placebo effect". For a drug to be considered for approval by a country's regulatory authorities there needs to be a "significant difference" between the active ingredient (drug) and the placebo. In this case, 50%-60% is significantly different from 25%-30%.
Researchers from the Northwestern University Feinberg School of Medicine believe that about half of all patients never get relief from antidepressants because their illness has been oversimplified and their medication is aimed at the wrong target. Professor Eva Redei explained that antidepressants are often targeting and treating stress, rather than the depression itself.
Medication plus psychotherapy is more effective - patients who receive a combination of antidepressant medication and psychotherapy tend to get better results with major depressive disorder compared to those who are on medication alone or have just psychotherapy, according to several studies.
A team from the National Institutes of Health's National Institute of Mental Health reported in Archives of General Psychiatry that adolescents with major depression who received a combination of medication and psychotherapy over a 36-week period had significantly superior improvements than patients of the same age who were receiving just one type of therapy. They noted that a higher percentage (15%) of those on fluoxetine (Prozac) alone had suicidal thoughts than those on cognitive behavioral therapy alone (6%) or combination treatment (8%).

Can I become addicted to an antidepressant?

Unlike nicotine, some illegal street drugs, tranquilizers and many painkillers, you do not need to keep raising the dose to get the same effect with antidepressants - so in that sense they are not addictive.
When somebody is weaned off an antidepressant they will not experience the withdrawal symptoms that you get when you are addicted to nicotine and try to give up smoking.
However, studies have shown that nearly one third of all patients on SSRIs and SNRIs experienced withdrawal symptoms when treatment stopped. Withdrawal symptoms lasted from two weeks to a couple of months.
Withdrawal symptoms reported included anxiety, dizziness, nightmares and/or vivid dreams, electric shock-like sensations in the body, flu-like symptoms, and stomachache. In the vast majority of cases, symptoms were mild. Severe cases are uncommon and are more likely to happen when patients come off Seroxat and Efexor. Doctors should wean patients off antidepressants gradually to minimize the risk of unpleasant withdrawal symptoms.
Is it withdrawal or illness recurrence? - If a patient finds it hard to cope some months after stopping antidepressant therapy, it is probably because their original illness or condition has come back, rather than a withdrawal problem.
SANE5 in Australia explains that antidepressants change the way you feel. "This means that if you stop taking the medication you may start to feel the way you did before the treatment. Some people confuse this with being addicted. Antidepressants are not addictive and you will not become dependent on them."

Can pregnant women take antidepressants?

The doctor and patient need to discuss fully the benefits and potential harms of coming off antidepressants during pregnancy. Some people really need the medication to be well. Ideally, a pregnant mother should take as little medication as possible.
The mother and doctor need to consider what the effect on the child would be if she came off the drug and became very ill. Other therapies should be discussed and considered, such as CBT (cognitive behavioral therapy), meditation, or yoga.
Risk of miscarriage - a team of medical investigators and pharmacists from the University of Montreal reported in CMAJ (Canadian Medical Association Journal) that taking antidepressants during pregnancy raises the risk of miscarriage by 68%. They added that up 3.7% of pregnant mothers use antidepressants during their first trimester.
High blood pressure - scientists from the University of Montreal, Quebec, Canada, reported in the British Journal of Clinical Pharmacology that using selective serotonin re-uptake inhibitors during pregnancy most likely raises the risk of pregnancy-induced hypertension (high blood pressure). The authors added that they had not established a causal link
Neonatal abstinence syndrome - a study at the Children's Medical Center of Israel, Petah Tiqwa, found that almost one third of infants whose mothers were on antidepressants while pregnant went through neonatal abstinence syndrome; withdrawal symptoms that include disturbed sleep, tremors and high-pitched crying. In some cases, their symptoms were severe.
A study using laboratory rats which were exposed to an antidepressant just before and after birth, found thatthey had considerable brain abnormalities and behaviors. The animals had been exposed to citalopram, a serotonin-selective reuptake inhibitor.

Can I take antidepressants if I am breastfeeding?

Some antidepressants get into the breast milk in only tiny amounts; examples include sertraline and nortriptyline. Within a few weeks after birth the livers and kidneys of babies are able to break down the medication's active ingredients effectively, as well as adults do.
The mother and doctor need to consider several factors:
  • The general health of the baby, is he/she premature, for example
  • The risk of the mother's mental condition returning
  • How much of the active ingredients gets into the breast milk (this varies, depending on the drug)
The Journal of Clinical Endocrinology & Metabolism published a study which found that antidepressant usage during pregnancy may delay lactation after childbirth; in other words, it may take longer for the mothers to be able to breastfeed. Mothers may need additional support to be able to successfully breastfeed. Co-author, Nelson Horseman, PhD, said "The breasts are serotonin-regulated glands, meaning the breasts' ability to secrete milk at the right time is closely related to the body's production and regulation of the hormone serotonin."

Taking antidepressants requires compliance, close monitoring and some perseverance

A sizeable minority of patients, between 40% and 50% of them, say their medications were not effective, even after having taken them for three months. There could be many reasons for this; possibly the wrong medication was chosen, the patient was not closely monitored enough, the treatment should have included other therapies, such as cognitive behavioral therapy, or poor compliance/adherence (the patient sometimes forgot to take his/her meds, did not take them at the right time, etc).
A Doctor consulting with a patient
Keeping in close contact with the doctor helps improve your chances. Possibly the dosage needs to be changed, or the doctor may eventually recommend switching to another medication. This will not happen if the patient does not go back to the doctor.
If there are going to be side effects, they will nearly always be present during the first couple of weeks, and then will gradually wear off. Patients should persevere, unless the side effects are too unpleasant. If this occurs, you should tell your doctor straight away.
The antidepressant needs to be taken according to instructions - if it says every day, it has to be every day, otherwise it will not be effective.
The majority of patients will feel no benefits during the first or second week. The full effect will not be present until after one or two months. Perseverance is vital.
Switch drugs or add another one - researchers from the University of Texas Southwestern Medical Center said that if your antidepressant is not working within six to eight weeks, your chances of recovery are considerably better if you either switch drugs or add another medication, compared to just giving up.


Most American pediatric patients do not complete their course - approximately half of all Medicaid-covered children and adolescents in Ohio do not complete their first three months of depression treatment, researchers from Ohio State University found. The authors added that non-compliance was greater among the teenagers.
Primary care physicians and psychiatrists say that the main reason people do not get better and their depression either returns or does not improve is that they stop too early, before any real benefits may be felt.

How long does an antidepressant treatment course last?

The Royal College of Psychiatry says that the majority of depressions resolve within about 8 months without treatment. People who stop taking their medication before 8 months risk a return of symptoms. Ideally, the patient should stay on the antidepressant for at least six months after feeling better. Patients who have had at least two attacks should carry on with the treatment for at least 24 months.
In more severe cases, when the depression regularly recurs, they may have to continue with their pharmacological treatment for several years.
Long-term antidepressant usage may worsen depression outcome - scientists from the University of Bologna, Italy, found that sometimes, long-term usage of antidepressants may make the person biochemically more vulnerable to depression. They added that in many cases there will be a poor response to pharmacological treatment.

Reducing the risk of the depression coming back

Some studies have shown that a healthy, well-balanced diet, plenty of exercise, and staying in touch with family and friends can reduce the risk of depression.
Disappointing findings regarding exercise and depression - a published in the BMJ (British Medical Journal)found that there was no difference in outcomes between depressed people who received "usual care" and those who received "usual care plus exercise".
People with mild depression may benefit from counseling.
Hypericum, which is made from St. John's wort, a herb, has been shown to help a number people with depression.
The National Center for Complementary and Alternative Medicine3, part of the US National Institutes of Health, says that St. John's wort may help some types of depression. However, it also warns that combining St. John's wort with certain antidepressants raises the risk of potentially life-threatening increases in serotonin. There is also the risk that the herb might reduce the efficacy of some prescription medications. It is important to tell your doctor or pharmacist if you plan on taking St. John's wort.
For those who suffer from SAD (seasonal affective disorder), sometimes known as "winter blues", a light box may help. The light box is switched on for a specific period each day and the patient sits in front of it. SAD is said affect some adults and teenagers during the winter months because of a lack of sunlight. Plenty of sunlight exposure helps maintain healthy levels of vitamin D. A study found that women with depression who were treated for vitamin D deficiency responded well and reported fewer depressive symptoms.
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