Antidepressant Medications

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Antidepressant Medications

Depression is usually treated with either medication or psychotherapy, or both.

Often, from a biological perspective, the causes of psychiatric disorders are called

"chemical imbalances" because it is believed that abnormal amounts or functions of chemicals in the brain produce the symptoms and changes in behavior usually observed. The sources of these imbalances can be either genetic or environmental.

It is likely that in most cases, the causes are multiple, including both genes and situational changes. For example, especially for depressed individuals who have several blood relatives with depression, genes are likely to be playing an important role in the source of the depression and even in the types of medications most likely to be beneficial. Other factors, such as stress-related environmental effects and learned changes in thought and behavior, are very frequently involved.

Accumulating evidence indicates not only that genes can affect environmental responses, but also that environmental factors and behaviors can modulate gene action.

The chemicals present in the brain that control its functions (thoughts, emotions, motivations, normal and abnormal behaviors) are called . There are a wide variety of these chemicals in the brain, and more are being discovered every year. Two of the earliest discovered and most important are and . These various substances are called neurotransmitters because they exist in neural tissue (brain and the rest of the nervous system) and transmit information between the nerve cells (called neurons). Information is passed in specialized regions between the cells called synapses when one neuron stimulates (or inhibits) the firing of another neuron.

This occurs when the first neuron releases neurotransmitter molecules, that in turn affect the second neuron. The effect of the neurotransmitter chemical on the second neuron occurs at specialized areas on the neuron called receptors.

One important early theory of the biological cause of depression suggested that there was too little serotonin, and/or too little norepinephrine, in the brains of depressed people. This theory originated in part from the discovery that all drugs that relieved depression increased the effects of serotonin or norepinephrine. In the brain, the effects of both serotonin and norepinephrine are turned off by of the neurotransmitter molecules from the into the first neuron, therefore stopping the effect on the second neuron. (For the system to work properly, it must turn on and turn off properly.) The primary mechanism by which drugs that treat depression work, is by decreasing the reuptake into the first neuron, leaving more to affect the second neuron. By the theory, this would relieve the effects of too little serotonin and/or norepinephrine. That is why many antidepressant drugs are called

"reuptake inhibitors" (for example, why drugs like fluoxetine-Prozac-are often called "SSRIs"-Selective/Specific Serotonin Reuptake Inhibitors). More recent theories suggest more complex mechanisms for how these drugs relieve depression

(and why they take weeks to do so), but reuptake blockade undoubtedly plays a role.

How well do antidepressants work in practice? They are used mainly for moderate or severe depressive symptoms. They can be used in combination with psychotherapy, which is often most effective. They typically take 1-3 weeks to have any benefit, and 1-3 months for full benefit. One-half to two-thirds of patients who are correctly diagnosed with major depressive disorder will respond to the first drug chosen, and 75% to 80% of patients will eventually respond if several different medications are given full trials. Overall, no type of antidepressant drug is more effective than any other, but the different types can

have different side effects, and different drugs sometimes are more or less effective for different individuals. Many patients will have more than one disorder

(co-morbidity). These individuals sometimes need additional treatment. Patients are more prone to relapse if they discontinue treatment before it is recommended

(usually at least 4-6 months). The more severe the depression (more severe symptoms, longer duration of symptoms, prior episodes of depression earlier in their lives, many blood relatives with the same disorder, co-morbid disorders such as substance abuse, anxiety, personality disorder) the longer treatment should last, even up to life-long. The major causes of lack of treatment response include inadequate medication dose or length of treatment, wrong , and patient nonadherence to treatment recommendations.

Treatments other than medications are available for depression. These include various methods of counseling and psychotherapy, so-called non-traditional treatment methods (such as herbal substances), and in more severe cases such methods as E.C.T. Placebos (substances or methods not known to have specific effects) produce improvement in about one-third of patients.

There are many sources of information about depression for patients and other interested individuals. Whether it is a book, a computer source, or advice of a friend, be open-minded but critical of the source and the information at the same time. Depression is a very common, and often quite debilitating illness, so there is a great deal of interest in the topic, but not always sufficient quality control for the claims made.

What are the symptoms of major depression?

The onset of the first episode of major depression may not be obvious if it is gradual or mild. The symptoms of major depression characteristically represent a significant change from how a person functioned before the illness. The symptoms of depression include:

 persistently sad or irritable mood pronounced changes in sleep, appetite, and energy difficulty thinking, concentrating, and remembering physical slowing or agitation lack of interest in or pleasure from activities that were once enjoyed feelings of guilt, worthlessness, hopelessness, and emptiness recurrent thoughts of death or suicide persistent physical symptoms that do not respond to treatment, such as headaches, digestive disorders, and chronic pain

When several of these symptoms of depressive illness occur at the same time, last longer than two weeks, and interfere with ordinary functioning, professional treatment is needed.

What are the causes of major depression?

There is no single cause of major depression. Psychological, biological, and environmental factors may all contribute to its development. Whatever the specific causes of depression, scientific research has firmly established that major depression is a biological, medical illness.

Norepinephrine, serotonin, and dopamine are three neurotransmitters (chemical messengers that transmit electrical signals between brain cells) thought to be involved with major depression. Scientists believe that if there is a chemical imbalance in these neurotransmitters, then clinical states of depression result.

Antidepressant medications work by increasing the availability of neurotransmitters or by changing the sensitivity of the receptors for these chemical messengers.

Scientists have also found evidence of a genetic predisposition to major depression.

There is an increased risk for developing depression when there is a family history of the illness. Not everyone with a genetic predisposition develops depression, but some people probably have a biological make-up that leaves them particularly vulnerable to developing depression. Life events, such as the death of a loved one, a major loss or change, chronic stress, and alcohol and drug abuse, may trigger episodes of depression. Some illnesses such as heart disease and cancer and some medications may also trigger depressive episodes. It is also important to note that many depressive episodes occur spontaneously and are not triggered by a life crisis, physical illness, or other risks.

How is major depression treated?

Although major depression can be a devastating illness, it is highly treatable.

Between 80 and 90 percent of those diagnosed with major depression can be effectively treated and return to their usual daily activities and feelings. Many types of treatment are available, and the type chosen depends on the individual and the severity and patterns of his or her illness. There are three well-established types of treatment for depression: medications, psychotherapy, and electroconvulsive therapy (ECT). For some people who have a seasonal component to their depression, light therapy may be useful. These treatments may be used alone or in combination. Additionally, peer education and support can promote recovery. Attention to lifestyle, including diet, exercise, and smoking cessation, can result in better health, including mental health.

Medication.

. It often takes two to four weeks for antidepressants to start having an effect, and 6-12 weeks for antidepressants to have their full effect. The first antidepressant medications were introduced in the 1950s. Research has shown that imbalances in neurotransmitters like serotonin, dopamine, and norepinephrine can be corrected with antidepressants. Four groups of antidepressant medications are most often prescribed for depression:

Selective serotonin reuptake inhibitors (SSRIs) act specifically on the neurotransmitter serotonin. They are the most common agents prescribed for depression worldwide. These agents block the reuptake of serotonin from the synapse to the nerve, thus artificially increasing the serotonin that is available in the synapse (this is functional serotonin, since it can become involved in signal transmission, the cardinal function of neurotransmitters). SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro), and fluvoxamine (Luvox).

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are the secondmost popular antidepressants worldwide. These agents block the reuptake of both serotonin and norepinephrine from the synapse into the nerve (thus increasing the amounts of these chemicals that can participate in signal transmission). SNRIs include venlafaxine (Effexor) and duloxetine (Cymbalta).

Bupropion (Wellbutrin) is a very popular antidepressant medication classified as a norepinephrine-dopamine reuptake inhibitor (NDRI). It acts by blocking the reuptake of dopamine and norepinephrine.

Mirtazapine (Remeron) works differently from the compounds discussed above. Mirtazapine targets specific serotonin and norepinephrine receptors in the brain, thus indirectly increasing the activity of several brain circuits.

Tricyclic antidepressants (TCAs) are older agents seldom used now as firstline treatment. They work similarly to the SNRIs, but have other neurochemical properties which result in very high side effect rates, as compared to almost all other antidepressants. They are sometimes used in cases where other antidepressants have not worked. TCAs include amitriptyline (Elavil, Limbitrol), desipramine (Norpramin), doxepin (Sinequan), imipramine (Norpramin,

Tofranil), nortriptyline (Pamelor, Aventyl), and protriptyline (Vivactil).

Monoamine oxidase inhibitors (MAOIs) are also seldom used now. They work by inactivating enzymes in the brain which catabolize (chew up) serotonin, norepinephrine, and dopamine from the synapse, thus increasing the levels of these chemicals in the brain. They can sometimes be effective for people who do not respond to other medications or who have “atypical” depression with marked anxiety, excessive sleeping, irritability, hypochondria, or phobic characteristics. However, they are the least safe antidepressants to use, as they have important medication interactions and require adherence to a particular diet. MAOIs include phenelzine (Nardil), isocarboxazid (Marplan), and tranylcypromine sulfate (Parnate).

Non-antidepressant adjunctive agents. Often psychiatrists will combine the antidepressants mentioned above with each other (we call this a

“combination”) or with agents which are not antidepressants themselves (we call this “augmentation”). These latter agents can include the atypical antipsychotic agents [aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine

(Seroquel), ziprasidone (Geodon), risperidone (Risperdal)], buspirone (Buspar), thyroid hormone (triiodothyonine, or “T3”), the stimulants [methylphenidate

(Ritalin), dextroaphetamine (Aderall)], dopamine receptor agonists

[pramipexole (Mirapex), ropinirole (Requipp)], lithium, lamotrigine (Lamictal), s-adenosyl methionine (SAMe), pindolol, and steroid hormones (testosterone, estrogen, DHEA).

What are the different kinds of antidepressants?

Antidepressants are put into groups based on which chemicals in the brain they affect. There are many different kinds of antidepressants, including:

Selective serotonin reuptake inhibitors (SSRIs) o citalopram (brand name: Celexa) o o o o escitalopram (brand name: Lexapro) fluoxetine (brand name: Prozac) paroxetine (brand names: Paxil, Pexeva) sertraline (brand name: Zoloft)

These medicines tend to have fewer side effects than other antidepressants. Some of the side effects that can be caused by SSRIs include dry mouth, nausea, nervousness, insomnia, sexual problems and headache.

Tricyclics o amitriptyline (brand name: Elavil) o desipramine (brand name: Norpramin) o o imipramine (brand name: Tofranil) nortriptyline (brand name: Aventyl, Pamelor)

Common side effects caused by these medicines include dry mouth, blurred vision, constipation, difficulty urinating, worsening of glaucoma, impaired thinking and tiredness. These antidepressants can also affect a person's blood pressure and heart rate.

Serotonin and norepinephrine reuptake inhibitors (SNRIs) o venlafaxine (brand name: Effexor) o duloxetine (brand name: Cymbalta)

Some common side effects caused by these medicines include nausea and loss of appetite, anxiety and nervousness, headache, insomnia and tiredness. Dry mouth, constipation, weight loss, sexual problems, increased heart rate and increased cholesterol levels can also occur.

Norepinephrine and dopamine reuptake inhibitors (NDRIs) o bupropion (brand name: Wellbutrin)

Some of the common side effects in people taking NDRIs include agitation, nausea, headache, loss of appetite and insomnia. It can also cause increase blood pressure in some people.

Combined reuptake inhibitors and receptor blockers o trazodone (brand name: Desyrel) o o o nefazodone (brand name: Serzone) maprotiline mirtazpine (brand name: Remeron)

Common side effects of these medicines are drowsiness, dry mouth, nausea and dizziness. If you have liver problems, you should not take nefazodone. If you have seizures, you should not take maprotiline.

Monamine oxidase inhibitors (MAOIs) o isocarboxazid (brand name: Marplan) o o phenelzine (brand name: Nardil) tranlcypromine (brand name: Parnate)

MAOIs are used less commonly than the other antidepressants. They can have serious side effects, including weakness, dizziness, headaches and trembling.

Taking an MAOI antidepressant while you're taking another antidepressant or certain over-the-counter medicines for colds and flu can cause a dangerous reaction. Your doctor will also tell you what foods and alcoholic beverages you should avoid while you are taking an MAOI. You should not take an MAOI unless you clearly understand what medications and foods to avoid. If you are taking an MAOI and your doctor wants you to start taking one of the other antidepressants, he or she will have you stop taking the MAOI for a while before you start the new medicine. This gives the MAOI time to clear out of your body.

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