Depression in Adults: Effective Treatments
Everyone has times they feel sad and don’t enjoy life. For some people the emotional pain becomes so severe or prolonged that it becomes a problem. This is depression. Because there seem to be different patterns of depression that respond to different treatment, psychiatrists have divided depression into categories.
Types of Depression
Major Depression is the most severe form of depression. It involves low mood or loss of enjoyment in most activities for two or more weeks. This is accompanied by such symptoms as change in sleep and appetite, loss of energy, loss of self-esteem, difficulty concentrating and preoccupation with death or suicide. In some cases depressed people become irrationally convinced that something terrible is happening to them, such as poverty or fatal disease. The depressed person may withdraw from friends and family, and be unable to work. Studies show that between 6 and 19% of the population will suffer from major depression at some time in their life. It appears to be a “biological” illness in that the tendency to develop this condition can run in families, that depression can occur for no apparent reason and when the person has experienced no significant changes in their life, and that the misery can resolve with medication treatment alone in some cases.
While symptoms are less intense than in Major Depression, Dysthymic Disorder lasts for years. In fact the low mood and associated symptoms must be present on most days for at least two years to qualify for this diagnosis. About 6% of the population will experience this form of depression.
There are several other important forms of depression. Adjustment Disorder with Depressed Mood involves a drop in mood in response to a specific stressful circumstance. Bipolar disorder involves low mood periods similar to Major Depression, but with periods of elevated or irritable mood as well. Depression can also occur as a biological reaction to certain physical illnesses (e.g. strokes affecting the left frontal cerebrum, hypothyroidism, pancreatic cancer) or to chemical substances (e.g. alcohol, methamphetamine, B-blocking antihypertensive medications).
The optimum treatment depends on the type of depression. Patients with Major Depression may be treated with medication, psychotherapy, or electro convulsive therapy (ECT). The choice depends on the symptoms (severity and type), patient preference and history of treatment response during prior depressive episodes. With more severe forms of Major Depression it is generally necessary to use either medication or ECT. Specific psychotherapies can be used along with medication, or as a sole form of treatment in the case of less severe forms of Major Depression.
Patients with Major Depression are usually treated with medication (about 70% of people respond well) or ECT (about 80% response rate). Psychotherapy may be an important adjunct to treatment. Psychotherapy can help the person to decrease the impact of the depressive symptoms and to sustain hope.
Patients with Dysthymic Disorder have historically been treated with psychotherapy alone. In recent years however, it has become apparent that more than half (50-60% response rate) of patients with Dysthymic Disorder will respond to most types of antidepressants (1). Since the medications that have been available in the past 10-15 years are relatively non-toxic, it is often worth trying antidepressant medication with psychotherapy, even when the depression seems related to psychological factors.
Psychotherapy approaches to dysthymic disorder include Cognitive Psychotherapy, Interpersonal Psychotherapy, and where conflicts are an important part of the problem, Psychodynamic Psychotherapy.
Cognitive Psychotherapy is based on the recognition that when people are depressed they think differently. Pessimism causes the depressed person to expect the worst, and to behave as if this were a certainty. This results in not trying new things (“it won’t work” or “I probably wouldn’t enjoy it”), in withdrawing from friends (“they will be bored with me”). Cognitive therapy helps a person to examine the distorted assumptions that go with depression, and that maintain the person thinking and acting in ways that keep them depressed.
Interpersonal Psychotherapy investigates the ways in which problems with relationships (role disputes, role transitions, unresolved grief and social deficits) can have a profound impact on mood and functioning.
Psychodynamic Psychotherapy explores the roots of adult dysfunction in unresolved childhood conflicts. By doing so it helps explain why the person would choose to do things that seem harmful to them. It permits a reevaluation of assumptions about oneself and others, so that the person can deal more effectively with others and themselves.
Antidepressant Medications appear to work by increasing the availability of certain chemicals in the brain. These chemicals, called neurotransmitters, are necessary for each nerve in the brain to send messages to other nerves. Several parts of the brain are important in maintaining our usual range of mood. The information needed to maintain mood is conveyed in part with chemical signals. In some forms of depression, these chemical signals may be too weak. Antidepressants can serve to strengthen the signal and help return the low mood to a normal range. The chemical messengers most commonly affected by these medications are serotonin (also called 5-hydroxytryptamine or 5HT) and norepinepherine. Often it takes two to four weeks for depression to respond fully to these medications, although some people may respond in a matter of days. About 70% of patients with major depression respond to
The first relatively safe and effective medications to treat depression became available over forty years ago. These were the tricyclics antidepressants, named for the presence of three rings in their chemical structure. They are just as effective as the most recently marketed antidepressants. The primary effect of most of the tricyclics antidepressants is to block the reuptake of norepinepherine and/or serotonin, but in contrast to the ‘selective’ medications, their effects are more diverse. They frequently block effects of other neurotransmitters like acetyl choline (causing dry mouth, blurry vision, constipation, urinary hesitancy urinary obstruction, heart palpitations), histamine (causing weight gain and sedation) and the a1-adrenergic (norepinepherine) receptor (causing low blood pressure on standing (dizziness, fainting and heart palpitations) and sexual dysfunction). They can cause heart arrhythmias and seizures (rarely in usual doses, but more commonly with overdoses). Thus, these medications can be more dangerous than the more recently introduced antidepressants, if taken as an overdose. This is of major concern since very severely depressed patients are at greatest risk to attempt suicide.
Attempts to find medications with fewer and less serious side effects, led to the discovery of other groups of medication that act more selectively. These include the “selective serotonin reuptake inhibitors” or SSRI’s: fluoxetine (Prozac), sertraline (Zoloft), fluvoxamine (Luvox), paroxetine (Paxil) and citalopram (Celexa); venlafaxine (Effexor; a selective serotonin and norepinepherine reuptake inhibitor), trazodone and nefazadone (Desyrel and Serzone, “serotonin modulators”), mirtazepine (Remeron, a serotonin and norepinepherine enhancer), and bupropion (Wellbutrin, a norepinepherine enhancer).
Another group of antidepressants is the “monoamine oxidase inhibitors” or MAOI’s. This group has been around about as long as the tricyclics antidepressants (1950′s). They can be very effective antidepressants, and for certain people can be the best treatment. But because of some potentially dangerous interactions with a number of foods and medications, they are not usually tried unless other treatments fail. They work by preventing the chemical messengers (serotonin and norepinepherine) between nerve cells from being destroyed by the enzyme monoamine oxidase. As with the other antidepressants, this increases the strength of the chemical signal. The problem with these medications is that there are a number of foods that contain a chemical, tyramine, which can raise blood pressure if it is not destroyed in the intestines before it gets into the blood stream. Normally the enzyme monoamine oxidase (present in the intestines as well as the brain) destroys the tyramine before it can be absorbed. However if a person takes the MAOI drugs, the enzyme is blocked and the result can be a dangerous elevation in blood pressure. Many of the foods that need to be avoided are high in protein and have been partially acted on by bacteria: aged cheese, hard sausages (pepperoni, salami), pickled herring. Also several varieties of wine and beer (but not distilled liquor) must be avoided. In addition there are several medications that should not be taken with the MAOI’s, including pseudoephedrine (Sudafed), diet pills with phenolpropanolamine (Dexatrim), and most other antidepressants.
Apart from the dietary and medication interactions, the MAOI’s have several possible side effects, including reduced blood pressure, sexual dysfunction, weight gain, sedation, dry mouth and constipation.
In addition to use as antidepressants these medications are also used to treat panic disorder and social phobia.
The two most commonly used MAOI’s are tranylcypromine (Parnate) and phenelzine (Nardil).
Specific Medications (2)
SSRI’s: fluoxetine (Prozac), sertraline (Zoloft), fluvoxamine (Luvox), paroxetine (Paxil) and citalopram (Celexa): These medications enhance the signals in nerves that transmit messages with serotonin. The some common side effects include nausea, diarrhea, headache, anxiety, insomnia or somnolence, tremor, sexual dysfunction, reduced motivation. When these occur they are generally not dangerous, but annoying. In addition, some of these SSRI’s are associated with a “discontinuation syndrome” if they are stopped abruptly. While also not dangerous, symptoms include nausea, anxiety, insomnia and headache. This occurs most frequently with paroxetine, fluvoxamine and venlafaxine (see below); it is much less common with sertraline, and rarely occurs with fluoxetine.
In addition to their use as antidepressants, SSRI’s have also been used to treat panic disorder, bulimia, obsessive compulsive disorder, excessive anger/aggression and premenstrual dysphoria.
Mirtazepine (Remeron): an a-2 adrenergic receptor antagonist (by blocking presynaptic inhibition of noradrenergic neurons it increases activity on noradrenergic neurons) and 5HT2 & 5HT3 blocker. Side effects include dry mouth, sedation and weight gain, but it is not frequently associated with sexual problems. It may have some anxiolytic effects. Typically, treatment begins at 7.5 mg and increases to the 15 to 45 mg/day range.
Bupropion (Wellbutrin): Its mechanism of action is unclear. It’s action may be mediated by it’s major metabolite, hydroxybupropion, a norepinepherine reuptake inhibitor. In addition to its use as an antidepressant, it may be used to treat nicotine addiction (smoking), attention deficit disorder and social phobia. Side effects most commonly seen include insomnia and nausea. It does not generally interfere with sexual functioning. An increased risk of seizures is seen with higher doses of the medication (>4% incidence at doses over 450 mg/day; <0.4% with lower doses).
Nefazadone (Serzone): This medication seems to act primarily on the serotonin system. Apparently it blocks postsynaptic serotonin receptors (5HT2A and 5HT2C), while a metabolite stimulates the 5HT2C receptor. It is thought that these actions indirectly stimulate the 5HT1A receptor. This antidepressant typically is used in doses from 300 to 600 mg/day. It seems to have anti-anxiety effects in addition to antidepressant actions. Side effects may include sedation, nausea, headache and decreased blood pressure (via a-adrenergic receptor blockade). There are seldom sexual side effects.
Venlafaxine (Effexor): In low doses (e.g. 75 mg/day), venlafaxine behaves much like an SSRI, with minimal effect on the norepinepherine system, however in the higher dose range (e.g. 375 mg/day) it also exhibits norepinepherine reuptake inhibition. This accords with the observed side effects: Nausea, vomiting and sexual dysfunction starting at low doses and increased sweating, dry mouth, increased blood pressure and heart rate at higher doses(3).
‘Tricyclic’ antidepressants: Members of this group include imipramine (Tofranil), amitriptyline (Elavil), doxepin (Sinequan), clomipramine (Anafranil), protriptyline (Vivactyl), trimipramine (Surmontil), nortriptyline (Pamelor), amoxepine (Asendin) and desipramine (Norpramin).
In addition to the antidepressant uses of these drugs, one or more of them have found use in treating: panic attacks ± agoraphobia (imipramine and clomipramine), obsessive compulsive disorder (clomipramine), attention deficit disorder (imipramine), primary incontinence (imipramine), neuropathic pain (doxepin, maprotiline, amitriptyline), migraine headaches (amitriptyline and doxepin), bulimia (imipramine and desipramine), generalized anxiety disorder (imipramine) and at times to other anxiety disorders (doxepin), insomnia (amitriptyline and doxepine) and ulcers (trimipramine and doxepin).
MAO inhibitors: The two most commonly used members of this group are phenelzine (Nardil) and tranylcypromine (Parnate). In recent years another MAOI, selegiline (Eldepryl) has been used in low doses (5-10 mg) to treat Parkinson’s Disease. At these lower doses it is selective enough that it does not required the dietary restrictions needed with the others, however in the doses that are effective treatment of depression (20-60 mg/day), the dietary restrictions must be followed. Some side effects seen with MAO inhibitors include: low blood pressure (feeling faint) when standing up, elevated blood pressure (if taken with certain foods or medications), daytime sedation and/or insomnia at night, constipation, dry mouth, weight gain and sexual dysfunction.
Electroconvulsive Therapy (ECT): This treatment can be highly effective for patients with severe depression. Some studies show an 80% response rate for treating major depression with ECT (4). Many studies comparing it to antidepressant medication in major depression show it to be at least as effective as medication, and possibly more so. The first reports describing the effectiveness of this treatment came out around 1940 (5). Modern ECT takes place in a medical setting where careful monitoring of the patient during treatment can take place. Prior to the treatments the patient must be carefully evaluated to look for any complicating physical problems. At the start of the procedure, a short-duration anesthetic is administered, followed by medications to relax the muscles. The psychiatrist then positions electrodes on the patient’s scalp and passes a current through them. This produces a seizure lasting 30-45 seconds. Because a muscle relaxant is used, there is generally little movement or chance of injury from muscle contractions. Because short-acting anesthetic agents are generally used, the patient may begin to regain consciousness within a matter of minutes after the treatment. The most common side effects of the procedure include headache and transient memory disturbances. Generally the patient receives two to three treatments a week, with the end point being complete recovery or a failure to show further improvement with additional treatments. It is fairly typical after the course of treatments conclude to use antidepressant medication or periodic “maintenance ECT” to prevent relapse. The problem of memory disturbance has been studied in detail. It depends to some extent on details of the treatment (electrode placement, electric current wave-form, frequency of treatments) and of the patient (advanced age, history of brain injury or brain disease). In general memory problems resolve entirely over a few weeks to a few months. Studies have shown no detectable memory deficit a year after the treatments.
St. John’s Wort (Hypericum perforatum) has been used extensively in Europe to treat mild-to-moderate severity depression. In Germany it accounts for 25% of antidepressant prescriptions. Attempts have been made to standardize this herb (e.g. 300 mg of plant extract containing 0.3% Hypericine). However, because it is not know what the active ingredient might be, there is really no way to know precisely the potency of a given batch. Most of the studies done on St. John’s Wort have been poorly designed (often vague or broad criteria for depression and for treatment response, lack of a placebo control group, comparison to low doses of pharmaceutical antidepressants). There have been some more recent studies that have attempted to address these shortcomings. Some of these studies show equal efficacy to prescribed antidepressants) (6) while others indicate St. John’s Wort is less effective (7). Some cautions now exist about the use of St. John’s Wort. It must be remembered that even though it comes from a flowering vine, St. John’s Wort is a drug. In addition to the fairly common side effect of nausea, it is known that St. John’s Wort hastens the metabolism of certain other drugs, thereby reducing the amount of the other medication in the patient’s body. These drugs include oral contraceptives, theophylline, cyclosporine, warfarin and the AIDS drug indinavir . The use of St. John’s Wort by patients depending on these medications can reduce the medication’s effect (which in some cases could be disastrous: at least two cases of incipient heart transplant rejection have been traced to the use of St. John’s Wort by transplant patients taking the anti-rejection drug cyclosporine). It may well be that St. John’s Wort will be shown to be an effective treatment for mild or moderate depression. However as we have discovered with all powerful and effective medications, there are inevitably some risks that must be known and understood to use the medication wisely.
Phototherapy: For some people, depressive episodes occur regularly at one time of year (generally mid-winter). This form of depression is often called Seasonal Affective Disorder (SAD) or Winter Depression. While this type of depression often can respond to medication, it has also been found to respond to bright light therapy. This typically involves the use of special lights (much brighter usual indoor illumination) before which the patient sits in the morning for perhaps 30 minutes each day. The advantage of bright light therapy over medication is that when it works, it usually has no side effects provided the lights are designed to produce the proper intensity (about 2000 lux). Interestingly SAD is seen more frequently as one moves away from the equator where winter day-length becomes shorter.
1.(Centre for Evidence-Based Mental Health Journal Vol. 1, #4, December 1998, Pg 111 or http://www.update-software.com/ccweb/cochrane/revabstr/ab001130.htm
2. Manual of Clinical Psychopharmacology 3rd Edition; A. Shatzberg, J. Cole and C. DeBattista; (1997) APA Press
3. Harvey, Rudolph and Preskorn Archives of General Psychiatry 2000; 57 (May): 503-509
4. American Psychiatric Association: The Practice of Electroconvulsive Therapy: Recommendations for Practice, Training, and Privileging. Task Force Report on ECT. Washington, DC, American Psychiatric Association, 1990
5. Cerletti U: L´elettroshock. Rivista Sperimentale Freniatria 64:209 310, 1940
6. Schrader, E. International Clinical Psychopharmacology 2000;15 (March):61-68
7. Gaster B, Holroyd J: St. John’s Wort for depression Archives of Internal Medicine 2000;160: 152-156