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Although about equally effective in a general population, some medications are more efficacious than others for specific types of depression. But the SSRIs do not always work, especially for more severely depressed patients, and they are more expensive.

Despite the widespread use of antidepressants, their actions are not fully understood.

They work in part by affecting the neurotransmitters signaling molecules in the brain norepinephrine, serotonin and dopamine, which are involved in regulating mood, primarily by blocking the reuptake of these neurotransmitters into the neurons that secrete them. Yet this action cannot fully explain the effects, and it is quite likely that the compounds drive a subsequent cascade of biochemical events.

Many people who do not respond to one antidepressant will respond to another or to a combination. New psychotherapy methods have proved as effective as medication, although they are still not as extensively tested [see box on next page].

The programs include interpersonal psychotherapy IPT , which focuses on problems in relationships and helps patients lift the self-blame common in de- SSRI. Selective serotonin reuptake inhibitors, such as Prozac and Paxil, block the reuptake of serotonin back into presynaptic neurons. They have replaced TCAs as the primary medication because they have fewer side effects and are less likely to prove fatal in an overdose. Nevertheless, side effects such as gastrointestinal and sexual problems can be disconcerting.

Indications that SSRIs may increase suicidal thoughts and actions in children and teenagers have led to mandatory warnings for these age groups in the U. Newer medications. More doctors are trying new drugs that affect multiple neurotransmitter systems or make use of mechanisms other than blocking reuptake.

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Examples include bupropion, venlafaxine, nefazodone and — S. Developed in the s, IPT has performed well in trials but has only begun to enter clinical practice. Studies do show, however, that when IPT is paired with medication, patients receive the best of both worlds: the quick results of pharmaceutical intervention and greater breadth in improving the quality of their interpersonal lives. Cognitive and behavioral therapies, collectively known as CBT, also compare well with medication in all but the most severely depressed patients—and they can benefit even those people if they are administered by experienced therapists.

Most exciting is that CBT appears to have an enduring effect that reduces risk of relapse and perhaps recurrence. Even the most effective of the other treatments rarely have this type of long-lasting benefit. Cognitive therapy is perhaps the most well established CBT approach. It teaches patients to examine the validity of their dysfunctional depressive beliefs and to alter how they process information about themselves.

Behavioral therapy had lost favor to the cognitive approaches, but it, too, has done well in recent trials and is undergoing a revival. Hollon is professor of psychology at Vanderbilt University and a past president of the Association for Advancement of Behavior Therapy. Thase is professor of psychiatry at the University of Pittsburgh Medical Center and chief of adult academic psychiatry at the Western Psychiatric Institute and Clinic there.

Psychotherapies for Depression havioral strategies and are often referred to as CBT. Recent variants such as mindfulnessbased cognitive therapy incorporate strategies based on mediation and acceptance; others such as well-being therapy try to enhance life skills and a sense of happiness in addition to reducing distress. And still others integrate cognitive and behavioral approaches with so-called dynamic and interpersonal strategies. These approaches are — S.


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Among patients who take antidepressants during treatment for acute symptoms, about half show a 50 percent drop in symptom scores on rating tests over the first four to eight weeks. About one third of those patients become fully well remission. Not all the improvement can be attributed to pharmacology, however.

In pill-placebo control experiments, placebos can achieve up to 80 percent of the success rate of active medication, probably by instilling in patients hope and the expectation for change. The placebo effect does tend to be less stable over time and smaller in magnitude in more severe or chronic depressions. A major problem with acute-phase therapy, however, is that many stop taking their medication— primarily because of side effects— before therapists can clearly tell if the agents are working.

Attrition rates from clinical trials are often 30 percent or higher for older medications such as the TCAs and around 15 percent for newer options such as the SSRIs. The newer psychotherapies appear to do as well as medication during the acute depression phase, although the number of studies is fewer and the findings are not always consistent.

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One typical study found that IPT alone was about as effective as medication alone with each better than a control condition and that the combination was better still. In general, medication relieved symptoms more quickly, but IPT produced more improvement in social functioning and quality of relationships. The combined treatment retained the independent benefits of each.

The TDCRP, as it is known, is perhaps the most influential study to date that compared medication and psychotherapy. In that trial, patients with major depression were randomly assigned to 16 weeks of IPT, CBT or the TCA imipramine, combined with meetings with a psychiatrist or a placebo plus meetings. Patients with less severe depression improved equally across conditions. Among more severely depressed patients, imipramine worked faster than IPT, but both were comparable by the end of treatment and both were superior to a placebo.

As for CBT, most of the published trials have found it to be as effective as medication in the acute phase. The most notable exception—the TDCRP— did find that cognitive therapy was less efficacious than either medication or IPT and no better than a placebo in the treatment of more severely depressed patients. Therapists help patients to understand life events that may have started their depression and to find ways to combat such episodes as well as reverse cycles of social withdrawal, fatigue and poor concentration.

IPT emphasizes that symptoms are the result of a mood disorder and not an outgrowth of personal failure, which lifts the guilt and selfblame common in depression. Cognitive and behavior therapies hold that mood disorders are caused or exacerbated by learned beliefs and behaviors—which can be unlearned or modified through experience.

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Most therapies blend cognitive and be- 30 Severity of Depression HRSD scale enthusiasm for cognitive therapy, even though no other study had produced such a negative finding. Today this conclusion appears to have been premature. More recent studies have found that CBT is superior to pill-placebos and is as good as an SSRI for more severely depressed outpatients. Antidepressants appear to reduce the risk for relapse by at least half.

It is unclear exactly how long patients must keep taking medication to pass from remission into full recovery, but current convention is to go for at least six to nine months. IPT during the continuation phase appears to prevent relapse nearly as well as medication, although studies in this regard are few. Recent investigations also suggest that if cognitive therapy is continued past the point of remission, it can reduce the risk for relapse. During the maintenance phase, medication is usually recommended for high-risk patients, especially those with multiple prior episodes.

Therapy can go on for years.

Scientific American Mind (Volume 14, Number 5, December 2004)

It does protect against recurrence. Even among recovered patients, though, the risk of recurrence off medication is at least two to three times greater. Given that there is no evidence that prior medication use does anything to reduce subsequent risk for recurrence, most physicians will encourage their high-risk patients to stay on medication indefinitely. Studies of maintenance IPT are few, but they generally support the notion that it, too, reduces risk of recurrence.

It has not been as efficacious as keeping people on medication, but the handful of studies have typically cut back the frequency of IPT to monthly sessions while maintaining medication at full, acute-treatment dosages. Patients treated to remission with CBT were only about half as likely to relapse after treatment termination as patients treated to remission with medication, and the CBT patients were no Combining medication nefazodone and psychotherapy gray reduced the intensity of symptoms furthest among chronically depressed patients in a study.

CBT appears to produce this enduring effect regardless of whether it is provided alone or in combination with medication during acute treatment and even if it is added only after medication has reduced acute symptoms. Further, indications are that this enduring effect may even prevent wholly new episodes recurrence , although findings are still far from conclusive. Given these trends, CBT may ultimately prove more cost-effective than medication.

Psychotherapy usually costs at least twice as much as medication over the first several months, but if the enduring effect of CBT truly extends over time, it may prove less costly for patients to learn the skills involved and discontinue treatment than to stay on medication indefinitely. It remains unclear whether other interventions such as IPT have an enduring effect, but this possibility should certainly be explored.

Our review of the treatment literature indicates that some forms of psychotherapy can work as well as medication in alleviating acute distress. Combined treatment, though more costly, appears to retain the advantages of each approach. Good medical care can be hard to find, and the psychotherapies that have garnered the most empirical support are still not widely practiced. Nevertheless, some kind of treatment is almost always better than none for a person facing depression.

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The real tragedy is that even as alternatives expand, too few people seek help. Frank et al.


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  • Keller et al. There are nine times as many glial cells in our gray matter as there are neurons. For 50 years, neuroscientists have maintained that glia merely provide support services to neurons: warding off pathogens, maintaining a healthy ion balance around the neurons and insulating them from electrical interference. Not only do glia talk with neurons, they communicate among themselves, aiding and abetting how our brains react, learn and remember.

    Ebook [Magazine] Scientific American. Vol. 290. No 5 2004

    Understanding more about how glia function may greatly alter our model of how the brain and mind work. Microglia in the brain act like immune system cells elsewhere in the body by protecting neurons from intruders. The latest research demonstrates that astrocytes— the most numerous of all glia— perform many different functions.

    Among other supportive jobs, astrocytes supply neurons with nutrients from blood vessels, they absorb neurotransmitters when needed to help shut down the neurons that are sending them, and they ensure that ion concentrations remain constant in intracellular spaces in the brain. But it has become increasingly clear that astrocytes also listen in on the signals passing from neuron to neuron and communicate with those neurons.

    Astrocytes talk with one another, too, along networks that parallel neural networks, using the same neurotransmitters that neurons use. Clearly, glia affect how neurons communicate— in other words, how we think and how our brains perform. And yet neurons and glia differ markedly in how they conduct information. Neurons send rapid electrical impulses, known as action potentials. Astrocytes use chemical messages, which are controlled by rising and falling concentrations of calcium ions. An increased concentration spreads throughout the cell like a human wave propagating through the stands at a baseball game— and often spills over to neighboring astrocytes through channels between the cells.

    Although they are dissimilar, the two types of cells sometimes use the same types of messenger molecules. Recently our neurobiology group in Bonn, working with Andrea Volterra of the University of Lausanne in Switzerland, demonstrated that astrocytes, when activated by the chemical messenger glutamate, release the same neurotransmitters that neurons release, using a similar molecular mechanism.

    By affecting how neurotransmitters carry signals across synaptic gaps among neurons and by releasing the same neurotransmitters to neurons and to one another, glia directly influence infor- www. Could they outthink neurons as well? After a neuron was stimulated to fire b, shown by bright lines , astrocytes began to light up, indicating they were sensing the message by absorbing calcium. After 10 and A B C D mation transfer in the brain. Astrocytes affect the signaling between adjacent neurons along a chain and, using their own network, also affect how neurons are triggered in distant parts of the brain.