(British Approved Name Modified, US Adopted Name, rINN)

International Nonproprietary Names (INNs) in main languages (French, Latin, and Spanish):

Note. The following terms have been used as ‘street names’ or slang names for various forms of sertraline: Z’s Zloft Zoomers.

Pharmacopoeias. In Europe.

European Pharmacopoeia, 6th ed. (Sertraline Hydrochlonde). A white or almost white, crystalline powder, ft exhibits polymorphism. Slightly soluble in water freely soluble in anhydrous alcohol slightly soluble in acetone and in isopropyl alcohol. Protect from light.

Adverse Effects, Treatment, and Precautions

As for SSRIs in general (see Fluoxetine). Menstrual irregularities and, rarely, erythema multiforme and pancreatitis have also been reported.

Sertraline should be used with caution in patients with hepatic or renal impairment reduced doses should be considered in patients with hepatic impairment.

Breast feeding. For comments on the use of SSRIs in breast feeding patients, see under Precautions for Fluoxetine.

Children. SSRIs are associated with an increased risk of potentially suicidal behaviour when used for the treatment of depression in children and adolescents under 18 years old for further details, see under Effects on Mental State in Fluoxetine.

Interactions

For interactions associated with SSRIs, see Fluoxetine.

Pharmacokinetics

Sertraline is slowly absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 4.5 to 8.4 hours after ingestion. It undergoes extensive first-pass metabolism in the liver. The main pathway is demethylation to inactive N-desmethylsertraline, a process that appears to involve multiple cytochrome P450 isoenzymes further metabolism and glucuronide conjugation occurs. Sertraline is widely distributed throughout body tissues and is about 98% bound to plasma proteins. The plasma elimination half-life of sertraline is reported to be about 26 hours steady-state concentrations are achieved after about one week with regular oral doses. Sertraline is excreted in about equal amounts in the urine and faeces, mainly as metabolites. Sertraline is distributed into breast milk (see Breast Feeding under Precautions in Fluoxetine).

Uses and Administration

Sertraline, a naphthaleneamine derivative, is an SSRI with actions and uses similar to those of fluoxetine. It is given orally as sertraline hydrochloride as a single dose in the morning or evening. Doses are expressed in terms of the base sertraline hydrochloride 56 mg is equivalent to about 50 mg of sertraline. In the treatment of depression, the usual initial dose of sertraline is 50 mg daily increased, if necessary, in increments of 50 mg at intervals of at least a week to a maximum of 200 mg daily.

The usual initial dose of sertraline in obsessive-compulsive disorder is 50 mg daily. In the treatment of panic disorder with or without agoraphobia, social anxiety disorder, and post-traumatic stress disorder, the usual initial dose is 25 mg daily increased after one week to 50 mg daily. Thereafter, doses in all these disorders may be increased, if necessary, in increments of 50 mg at intervals of at least a week to a maximum of200mg daily.

Sertraline is also given for the treatment of obsessive-compulsive disorder in children and adolescents aged 6 years and over. In children aged 6 to 12 years the usual initial dose is 25 mg once daily adolescents may be started on 50 mg once daily. Increases in doses, if necessary, are similar to those in adults however, the lower body-weights of children should be considered in order to avoid excessive doses.

In the treatment of premenstrual dysphoric disorder, sertraline is given in an initial dose of 50 mg daily either throughout the menstrual cycle or during the luteal phase only, as appropriate. Doses may be increased by 50 mg each menstrual cycle up to a maximum of 150 mg daily for continuous dosing or 100 mg daily when dosing during the luteal phase only. Those patients who require 100 mg daily during luteal phase-only dosing should initially be given 50 mg daily for the first 3 days of each luteal phase dosing period.

Once the optimal therapeutic response is obtained dosage should be reduced to the lowest effective level for maintenance.

Reduced doses are recommended in patients with hepatic impairment, see below.

Sertraline should be withdrawn gradually to reduce the risk of withdrawal symptoms.

Administration in hepatic impairment. The clearance of sertraline was reduced in patients with liver cirrhosis, in a single-dose pharmacokinetic study. US licensed product information states that in a small group of patients with chronic mild impairment (Child-Pugh scores of 5 to 8), given 50 mg daily for 21 days, exposure to sertraline was about 3 times that found in subjects with normal hepatic function. It also states that the effects of sertraline have not been studied in moderate and severe impairment. If sertraline is to be used in patients with hepatic impairment, it suggests that the drug should be used with caution and given at a lower dose or less frequently. UK product information considers sertraline to be contra-indicated in significant hepatic impairment, because of insufficient clinical experience.

Anxiety disorders. Sertraline has been given in a variety of anxiety disorders including obsessive-compulsive disorder, panic disorder, social anxiety disorder (see under Phobic Disorders), and post-traumatic stress disorder.

Depression. As discussed on site, there is very little difference in efficacy between the different groups of antidepressant drugs, and choice is often made on the basis of adverse effect profile. SSRIs such as sertraline are widely used as an alternative to the older tricyclics as they have fewer adverse effects and are safer in overdosage. References.

Headache. For reference to the use of SSRIs, including sertraline, in the management of various types of headache, see under Fluoxetine.

Premenstrual syndrome. Sertraline throughout the menstrual cycle has produced beneficial effects in controlling both the psychological and somatic symptoms of women with premenstrual syndrome. Giving sertraline solely during the luteal phase was also of benefit.

Sexual dysfunction. Impotence or ejaculatory problems have been reported as adverse effects of SSRIs for the use of these effects as a potential form of management for premature ejaculation see Fluoxetine.

Preparations

Proprietary Preparations

Argentina: Anilar, Atenix, Bicromil, Celonfex, Deprecalm, Insertec, Irradial, Serlina, Servantax, Vunot, Zoloft

Australia: Eleva, Setrona, Xydep, Zoloft

Austria: Gladem, Sertrex, Tresleen

Belgium: Serlain

Brazil: Assert, Novativ, Sercerin, Serenata, Seronip, Tolrest, Zoloft

Canada: Zoloft

Chile: Altruline, Deprax, Eleval, Emergen, Implicane, Lowfin, Sedoran, Serivo, Seronex, Sertac, Tralinser

Czech Republic: Adjuvin, Apo-Sertral, Asentra, Serlift, Setaloft, Stimuloton, Zoloft

Denmark: Zoloft

Finland: Zoloft

France: Zoloft

Germany: Gladem, Sertra, Zoloft

Greece: Certorun, Enidap, Neurosedine, Zoloft, Zolotrin

Hong Kong: Stimuloton, Zoloft

Hungary: Asentra, Gerotralin, Serlift, Serlosane, Sertadepi, Sertagen, Sertwin, Stimuloton, Zoloft

India: Inosert, Serdep, Serta, Xsert

Indonesia: Antipres, Deptral, Fatral, Fridep, Nudep, Serlof, Sernade, Zerlin, Zoloft

Ireland: Depreger, Lusert, Lustral, Serimel, Serlan, Sertraniche

Israel: Lustral

Italy: Tatig Zoloft

Malaysia: Serlift, Zoloft

Mexico: Aleval, Altruline, Aluprex, Deptral, Prosertin, Serolux, Sertex

The Netherlands: Asentra, Zoloft

Norway: Zoloft

New Zealand: Zoloft

Philippines: Serenata, Zoloft

Poland: Asentra, Luxeta, Sertahexal, Setaloft, Setaratio, Stimuloton, Zoloft, Zotral

Portugal: Zoloft

Russia: Asentra, Serenata, Stimuloton, Torin, Zoloft

South Africa: Serdep, Serlife, Sertzol, Zoloft

Singapore: Zoloft

Spain: Altisben, Aremis, Besitran, Depesert, Sealdin

Sweden: Zoloft

Switzerland: Gladem, Zoloft

Thailand: Zoloft

Turkey: Lustral, Selectra, Seralin, Serdep

UK: Lustral

USA: Zoloft

Venezuela: Conexine, Lusedan, Satil, Serline, Serolux, Tialin, Zoloft

Multi-ingredient

India: Restyl, Forte, Restyl Plus.

A meta-analysis compared the efficacy of sertraline (Zoloft) (N = 218), amitriptyline (N = 214), and placebo (N = 214) in two outpatient studies. The results showed similar efficacy of sertraline (Zoloft) and amitriptyline in reducing both depression and anxiety. Amitriptyline was not tolerated as well as sertraline (Zoloft) and had a greater overall incidence of side effects. There was a higher incidence of anxiety and agitation with amitriptyline in the high anxiety subgroup, and a higher incidence of agitation associated with amitriptyline in the low anxiety subgroup.

Sertraline has also been compared with newer antidepressants in mixed anxiety depression. Sertraline and nefazodone were studied in 41 patients with anxious depression. All subjects met DSM-III-R criteria for major depression, had minimum Hamilton Depression Rating scores of 18 and Hamilton Anxiety Scale scores of 21 at baseline. Twenty-one also met DSM-III-R criteria for panic disorder. The patients were treated with flexible doses of nefazodone (200-600 mg/day) or sertraline (Zoloft) (50-200 mg/day) for 6 weeks. There were no significant differences in outcome between drugs and no significant treatment differences between patients with or without concomitant panic disorder. Aguglia and colleagues (1993) conducted an 8-week multi-centre comparison of sertraline (Zoloft) and fluoxetine (Prozac) in 108 patients with DSM-III-R major depression. Again there were no significant differences in efficacy between the two treatment groups in either anxiety or depression.

The large epidemiological studies that have been carried out in recent years have drawn attention to the high rates of comorbidity of psychiatric disorders in the general community. Major depression is known to have a high comorbidity with separate anxiety disorders and a problem can arise in attributing certain anxiety symptoms as part of either the depression or the anxiety disorder. The overlap of major depression and an anxiety disorder where both conditions satisfy the full diagnostic criteria is perceived as comorbidity. In this case separate diagnoses may be considered. The overlap of major depression and anxiety disorders, where neither disorder satisfies the full criteria, has come to be known as mixed anxiety depression (MAD). This chapter attempts to address the degree of overlap which is so confusing for the clinician and to assess the data relating the role of selective serotonin reuptake inhibitors (SSRIs) in treatment.

Anxious depression or comorbid anxiety and depression

Mixed anxiety depression is a common but poorly defined condition with multiple possible aetiologies. Both anxiety and depression may occur as a symptom of or reaction to a primary psychiatric or medical disorder. The concept of major depression includes a variety of subgroups, including the more severe (psychotic features, melancholia) and chronic subtypes. Anxiety disorders are classified according to whether and how the anxiety is limited to particular situations (phobias, compulsions), thoughts (obsessions) or times (panic attacks). Generalized anxiety disorder (GAD) may be thought of as chronic anxiety which is not limited to any of these dimensions. Some basic researchers believe that anxiety and depression exist on a continuum and that depression may represent under-activity of serotonergic pathways while anxiety results from over-activity in serotonergic neurones.

There are two general meanings for mixed anxiety depression. One is the depressed patient who has signs or symptoms of an anxiety disorder which does not meet the threshold for a separate diagnosis, such as the patient with panic attacks which do not occur often enough or with the requisite number of symptoms to be diagnosed as panic disorder. The other is the patient with generalized anxiety disorder who intermittently fulfils criteria for major depression. Mixed anxiety depression also appears as an experimental diagnosis in DSM-IV (Table: Research criteria for mixed anxiety depressive disorder (DSM-IV)). Its anxiety symptom criteria are very similar, and in some cases identical, to those for GAD. However, DSM-IV requires that the disorder does not meet, and never has met, criteria for generalized anxiety disorder, major depression, dysthymic disorder and/or panic disorder. This is a problem, especially because the symptom threshold for dysthymic disorder is so low (requiring only two symptoms) that chronically depressed and anxious patients will almost never meet criteria for mixed anxiety depression. One might summarize this by saying that mixed anxiety depression (MAD), as it is currently regarded, is an admixture of a subsyndromal depressive disorder with a subsyndromal anxiety disorder. In a sense it is a testament to the importance of MAD that it has received as much research attention as it has despite this lack of satisfactory diagnostic criteria.

Table: Research criteria for mixed anxiety depressive disorder (DSM-IV)

Anxiety symptoms in depression

The scales employed for rating the severity of depression reflect the nature of these anxiety symptoms as integral to the depression. The scores on these anxiety items are seen to reduce as the depression improves and the items have good face validity in depression. For example, the Hamilton Scale for Depression (Hamilton, 1960) includes items to measure agitation, somatic anxiety and psychic anxiety. Three items that measure sleep disturbance and an item to assess the phenomenon of depersonalization feelings also form part of the scale. Moreover, it can be argued that the items for assessing obsessional symptoms and hypochondriasis also register anxiety symptoms. Most studies of the efficacy of various treatments for depression have shown that the symptoms measured by these anxiety items in the scales improve at the same rate as other symptoms of depression.

Some of the items in the Hamilton Rating Scale are more sensitive to treatment change than others and Hamilton himself recognized that the depersonalization and obsessional items, which are less sensitive, should be used more appropriately for diagnostic purposes only.

SSRI in the Treatment of Anxiety Symptoms Within Depression

Some treatments are acknowledged to be more effective than others in treating particular anxiety symptoms that occur with depression. The items that measure disturbed sleep improve more rapidly in response to sedative antidepressants with marked histaminergic receptor properties such as the sedative tricyclic antidepressants or mianserin. This has been shown in a number of comparisons with non-sedative antidepressants such as the selective serotonin reuptake inhibitors. However, the advantage seen with the sedative antidepressants, which is more evident at the start of treatment, tends to diminish as the sleep improves as part of the general improvement of the depression in response to SSRIs. By the end of the acute treatment period, the advantage of the sedative antidepressants on sleep is no longer evident. On the other hand, the negative effects on psychomotor function of the histaminergic activity become apparent with daytime drowsiness and the need to desist from driving cars or operating heavy machinery.

The early effect of anxiolytic drugs on disturbed sleep and certain other anxiety, symptoms in depression has been reported but an antidepressant effect cannot be attributed to these drugs merely on these grounds. The studies of benzodiazepines in the treatment of depression show their effects on improving the sleep items and anxiety but also show that they are less effective, or not effective at all, in improving other features of depression, and it is for this reason that, independently of the associated long-term problems of tolerance and dependence, benzodiazepines are not licensed or recommended for the treatment of major depression. Some studies have reported an increase in paradoxical aggression with benzodiazepines, possibly mediated by a mechanism involving disinhibition, and this characteristic makes these drugs unsuitable for depression, where there is an elevated risk of suicide attempts.

The selective advantages of selective serotonin reuptake inhibitors (SSRIs) in treating the anxiety symptoms of depression compared with sedative tricyclic antidepressants came as a surprise. Zimelidime, an early non-sedative SSRI that was withdrawn from the market, was found to be more effective than amitriptyline in treating the anxiety symptoms of depression in a 6-week treatment study. This finding raised the possibility that serotonin reuptake might have a special beneficial effect on the symptoms of anxiety within depression. Subsequent analysis for paroxetine (Paxil) and fluvoxamine (Luvox) have confirmed this hypothesis, with a differential advantage in treating anxiety symptoms in depression reported for the SSRIs compared with reference tricyclic antidepressants. These observations led to the hypothesis that SSRIs might have particular advantages in treating separate anxiety disorders, such as panic disorder and social phobia.

The first generation of antidepressant medication included tricyclics (TCAs) and monoamine oxidase inhibitors. A number of investigators have shown these drugs to be helpful in the treatment of anxious depression. Several trials have also shown TCAs to be equivalent or even superior to benzodiazepines in the treatment of this syndrome. SSRIs improved over tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) in two main areas: tolerability and safety. However, anxiety and agitation have been reported as occasional side effects with all selective serotonin reuptake inhibitors, which might lead to reluctance to use these agents in anxious depression. A review of the available data concerning the use of SSRIs in anxious depression, especially relating to whether baseline anxiety is a poor prognostic sign, is therefore timely.

The first line of evidence is indirect. It stems from the observation that patients with anxiety disorders often have concomitant depressive symptoms. There is considerable direct evidence of the efficacy of the SSRIs in anxiety disorders. All four SSRIs approved for marketing in the USA have shown sufficient efficacy to garner an official indication for at least one anxiety disorder, obsessive-compulsive disorder (OCD). Paroxetine (Paxil) and sertraline (Zoloft) are also indicated for the treatment of panic disorder (PD). While patients with bona-fide major depression are usually excluded from trials of an antidepressant in an anxiety disorder, it is likely that a substantial number of the subjects in OCD and PD trials had clinically significant depressive symptoms.

Filteau and colleagues analysed data from 10 studies of SSRIs (sertraline (Zoloft); zimelidine; fluvoxamine (Luvox); fluoxetine (Prozac)); selective noradrenergic uptake inhibitors — desipramine, maprotiline, oxaprotiline; mixed uptake inhibitors — amitriptyline, imipramine (Tofranil); and partial 5-HT2 antagonists — ritanserin, trazodone (Desyrel), nefazodone. The data showed no differences between the efficacy of these classes in agitated or retarded depression. In a subsequent analysis the same investigators found that SSRI responders tended to be initially more anxious and agitated than non-responders.

Answer. I would need to know more about your medication regimen; i.e., do you take the 200 mg of Serzone as a single dose or in two or three doses? At what times of day? If you are now taking the Serzone as a daytime dose, I would try shifting most or all of it to bedtime. Splitting up the total dose into 2 small (25 mg) doses and taking the remaining 150 mg at bedtime might work for some patients, without compromising efficacy. If you are already taking the Serzone in this way and are still feeling heavily sedated all the time, there are two equally reasonable options, in my view:

1. Switch to a less sedating agent (e.g., fluoxetine [Prozac] or sertraline [Zoloft]); or

2. Add a small amount of a stimulating agent to the Serzone, such as methylphenidate (Ritalin), bupropion (Wellbutrin) or caffeine. Caffeine, however, may exacerbate anxiety in some patients.

Some patients may tolerate an alternating schedule of, say 200 mg of Serzone one day, 150 mg the next, etc. Have you tried cutting down the Serzone by just 25 mg/day? It may be that if you can cut it down to the point that you no longer feel so drowsy, a small amount of Wellbutrin (e.g., 37.5 mg per day) could be added to augment the Serzone’s antidepressant effect–Wellbutrin does not have very good antianxiety properties. If the first option is used, I would start very low with the Prozac or Zoloft dose, in order to avoid initial worsening of anxiety; e.g., 5 mg per day of Prozac or 12.5-25 mg of Zoloft. You might need to buy a pill-cutter.

Which path to take would depend, in part, on whether you wanted to accept he risk-benefit ratio of a second (augmenting) agent, vs. the risk-benefit ratio of trying a new and hence uncertain, medication. My general rule is “build on strength.” Try to work with and around the first successful agent, if possible. By the way, are you certain that your TSH is now normal? (In most labs, below 4.5-5.0.) Borderline hypothyroidism can certainly contribute to low energy and delay antidepressant response.

Answer. I admire your tenacity, after all these complications with your treatment. So, let’s go through each of your questions and see if it leads to some treatment options to discuss with your doctor. First, I think buspirone augmentation can be helpful, particularly if there is an anxiety component to the depression. In fact, there are studies showing that buspirone alone, and in high doses (at least 50 mg/day) has antidepressant properties. Pindolol studies have yielded mixed results, and this may vary from SSRI to SSRI, but I think the risks are so minimal that it might be worth trying in your case. Other medications to consider as augmenters to SSRIs would include methylphenidate (Ritalin), which works well, in my experience, but could be overstimulating to you (if it were used, I’d start with 2.5 mg per day and hold it there for a week). Alternatively, you (with your doctor’s approval, of course) could try stopping the tyrosine for a week or two, then re-starting it. Sometimes this strategy works with the SSRIs as well, though some patients may experience mild-to-moderate withdrawal symptoms (flu-like symptoms) when a short-acting SSRI (Paxil, Zoloft) is suddenly stopped–so a tapering period might be better, followed by 1-2 weeks off, then a restart.

Another option would be to add a dopamine agonist, such as pergolide. I have seen this help in one case of very resistant depression. Here, too, I’d start low, and go slow with the dose. The combination of the MAO-B inhibitor selegiline (L-deprenyl) in combination with phenylalanine (another amino acid precursor) has been reported helpful. To use L-deprenyl, you must be off Zoloft for at least two weeks. You did not mention Serzone…if you haven’t tried this, it could be used in low doses in combination with the Zoloft, or as a single agent in much higher doses. Or, Serzone could be used in combination with most of the other agents mentioned above, except an MAOI. I don’t know if you’d consider treatment in Canada, but they do have a unique MAOI up there–moclobemide–that is not available in the States. It might work for you, even though two previous MAOIs did not. Moclobemide can usually be obtained via a cooperative arrangement between your doctor and one up in Canada. Then, there’s always St. John’s Wort, but we know so little about how well this works, or if it can be combined safely with standard antidepressants, that I can’t really recommend it.

Since you have been through the pharmacologic ringer, I think you should at least consider something that we know does work, and that is ECT. This is a safe and very effective treatment for major depression, and can be used on a maintenance basis.

As to the mechanism of “poop-out” – the undignified name says a lot about our state of knowledge. It doesn’t really fit the usual definition of tolerance since dosage increases may or may not help (with tolerance, an increase in dose virtually always – by definition – brings about a renewed response). Dopamine depletion from the SSRI is plausible, and goes along with the observation that some patients who experience this fading out of SSRI effects also experience a sort of emotional flattening and decreased response to rewarding stimuli (e.g., sex, good times, etc.). Since the reward system is mediated in large part by dopamine, this all hangs together. That may be why methylphenidate (Ritalin), which has dopamine enhancing properties, sometimes restores the SSRI response. On the other hand, the apparent success of pindolol – which basically unlocks the valve on the neuron that produces serotonin – suggests that serotonin slow down may underlie this loss of SSRI effect. I don’t think it is a pharmacokinetic effect in most cases. I do wish you and your doctor the best in dealing with your problem, and don’t give up!

This study, published in the journal “Clinical Therapeutics,” reveals that sexual dysfunction caused by antidepressants affects more people than previously expected, and the problem may be more common in patients taking certain types of drugs than others. In this placebo-controlled comparison of sertraline (Zoloft) and bupropion SR (Wellbutrin SR) in 355 patients with moderate to severe clinical depression, investigators found that orgasm dysfunction was more prominent in patients taking sertraline than in those taking bupropion SR or placebo.

In fact, after only one week of treatment, more patients taking sertraline reported orgasm dysfunction compared with bupropion SR or placebo. By the end of the study, 41 percent of patients taking sertraline reported orgasm problems. There was no significant difference in orgasm dysfunction between bupropion SR (15 percent) and placebo (eight percent).

Sertraline is a selective serotonin re-uptake inhibitor (SSRIs). Previous research has identified an association between SSRIs and sexual problems, including lack of orgasm, impaired erection, and delayed ejaculation. Researchers suggest that the serotonin effect of SSRIs might account for the negative effects on sexual function. Unlike sertraline, bupropion SR is not an SSRI and has no appreciable effect on serotonin.

The authors assert that depression itself can take a toll on relationships, and sexual dysfunction caused by some antidepressant treatments may further affect intimate relationships and adversely influence recovery. They suggest that the under-reporting of adverse sexual side effects may be due to shame or lack of knowledge on the part of patients, as well as reluctance by health-care providers to broach the subject. They stress that side effects should be acknowledged, and that open communication about any adverse medication effects is critical to successfully treating depression.

Researchers from the University of Oregon Health Sciences Center conducted a study of 10,000 people, 5,000 with Type II diabetes and 5,000 without it. The two groups were similar in other ways such as age and gender. The team hoped to answer three questions:

· Are diabetics more likely to be depressed than those who don’t have diabetes?
· What types of medications are depressed diabetic people likely to be taking?
· What are the costs of treating a person with diabetes, depression, or both?

They found that 62 percent of diabetics are more likely to be depressed than people without the disease. Among diabetics, those who are depressed are more likely to be taking insulin than managing their diabetes through diet and oral medications.

Diabetics are less likely to be taking antidepressant drugs. Of those who are being treated, most are on the same medications as any depressed patient—serotonin re-uptake inhibitors, such as Prozac, Zoloft, or Paxil. They also were taking more tricyclic antidepressants, such as Elavil. However, the researchers were uncertain if they were taking the antidepressants at the higher doses needed to treat depression or at the lower doses used to treat peripheral neuropathy, a common complication of diabetes.

As for costs, depressed people use more services and spend more money than average, whether or not they also have diabetes. In fact, it costs about the same amount to treat a diabetic without depression as it does to treat a depressed person without diabetes. Having both diseases increases costs considerably.

Treating the depression was shown to increase an individual’s adherence to his or her treatment plan, improve blood glucose control, as well as improve the individual’s psychological outlook.

From any perspective, untreated depression in Type II diabetes carries a high cost, financially, physically, and mentally.

Answer. Your story, unfortunately, echoes those of millions of individuals who suffer from severe, major depression. Some day, you may look back at what happened following your suicide attempt and feel that you were given a second chance to succeed at life. While I don’t have any magic solutions for you, I do want to offer you the perspective I have gained after having treated many hundreds of such patients.

First: Depression is a treatable and reversible condition, even when several therapies or medications have failed. There are still many treatments that could be tried and which I have seen work. It might be frustrating, but not all treatments are beneficial to an individual patient. You should talk to your psychiatrist about both your ongoing feelings of hopelessness and possible trials on some of the newer antidepressants, such as Effexor and Remeron. And, whatever you may have heard about ECT (electroconvulsive therapy), do not exclude this as a treatment option! I have seen ECT work for people who were virtually at death’s door. It is safe and very effective.

Second: In all my years of treating depressed patients and working with their families, I have never seen a single instance in which the family truly felt they would be better off without their depressed family member. That’s right, not once. This belief is virtually always a symptom of severe depression. In fact, suicide is usually a devastating emotional blow to a family, from which recovery is extremely difficult. Some families never recover from losing a loved one in this way.

Third: You are not alone. If you have not yet joined the National Depressive and Manic Depressive Association (NDMDA), I would urge you to do so. They provide support and peer counseling for thousands of individuals with depression; you can call 800-826-3632 for local referrals. You can also contact the National Mental Health Self-help Clearinghouse (800-553-4539). These groups should supplement, not replace, the help you are already receiving. Also keep in mind that the Samaritans provide 24-hour anonymous telephone counseling for suicidal individuals (ask your telephone operator for the number).

Finally, depending on your spiritual and religious orientation, consider some form of pastoral counseling; not as a replacement, but as a supplement to your therapy. I know it may be hard for you to believe there is a light at the end of the tunnel, but I hope you can believe that I believe that. Good luck…

Answer. Well, the media are often ahead of the scientists on these things, but I must say I am very skeptical about the 5-HTP story (although I did not see the Prime Time piece). By the way, 5-HTP is the precursor chemical for serotonin, which as you probably know is the neurotransmitter heavily involved in depression, appetite regulation, pain perception and sleep. In the first place, very few clinicians, to my knowledge, are prescribing or recommending 5-HTP to patients, at least among psychiatrists. Thus I suspect we are hearing about a handful of “testimonial” cases rather than seeing the results of methodical research or even clinical case reports. In fact, I didn’t find a single clinical case report or recent controlled study of 5-HTP for the uses you mention in the professional literature within the past 5 years!

However, there was one report in the British Journal of Psychiatry (July 1985 pp. 16-22) comparing the L isomer of 5-HTP with a classic antidepressant called tranylcypromine (termed an MAO inhibitor). These patients had not responded to several antidepressant medications, including SSRI-type antidepressants like Luvox (fluvoxamine). Of 17 patients given L-5-HTP, none responded. In contrast, 15 of 26 responded to tranylcypromine. The authors concluded that L-5-HTP was not therapeutically effective in such refractory patients. Of course, the possibility remains that milder cases of depression may respond to 5-HTP.

A precursor of 5-HTP, tryptophan, was used for many years as a sleeping aid, before being removed from the U. S. market after contaminated batches caused serious muscle problems. Serotonergic agents in general are thought to reduce carbohydrate craving and promote weight loss. However, experience with the SSRI (selective serotonin reuptake inhibitor) group of antidepressants – Prozac, Zoloft et al – suggests that while they may initially take off a few pounds, the weight creeps back up over a year or two.

5-HTP is an interesting agent, and is used in research settings to “probe” the serotonergic system. However, I think it is far too early to conclude that it is safe and effective for any of the uses you mentioned.

Panic disorders respond well to psychotherapy, drug treatment and a combination of the two, according to one of the largest studies of the condition.

Panic disorder affects several million Americans, crippling them with recurrent bouts of profound anxiety and physical symptoms that can include chest pain and pounding, as well as rapid heartbeats and shortness of breath. Many people also feel that, in the midst of an attack, they’re in danger of dying.

Perhaps it’s understandable, then, that people with this condition often feel there’s no hope of treatment. Fortunately for them, they’re wrong.

This conclusion won’t come as a surprise to specialists, who’ve been treating the condition with drugs and psychotherapy for many years. But, the researchers say, it should reinforce the message that panic disorder is a real diagnosis, and one that can be brought under control. Their findings appear in this week’s issue of the Journal of the American Medical Association.

Boston University researcher David Barlow and colleagues at three other clinics treated 312 patients from 1991 to 1998. Participants received one of five treatments: up to 300 milligrams a day of the antidepressant imipramine; a combination of imipramine and cognitive-behavioral therapy [CBT]; CBT alone; CBT plus a placebo; or a placebo alone.

Cognitive-behavioral therapy [CBT] tries to give people more control over their runaway fears by helping them recognize and stave off impending attacks through breathing exercises, desensitization techniques and other devices.

Participants received treatment once a week for three months. If they showed improvement, their treatment was eased back to once a month over a six-month maintenance period. They then were observed for an additional six months.

Using one psychiatric yardstick, known as the Panic Disorder Severity Scale, both the drug and psychotherapy treatments scored better than no treatment at reducing symptoms of panic disorder during the first phase of the study. However, neither bested the placebo when measured on another yardstick, the Clinical Global Impression Scale.

Among the people who improved during the first three months, both treatments were definitively better on each scale than the placebo during the maintenance stage. And the combination of the two was more effective than either treatment alone.

The researchers note, however, that more participants abandoned imipramine than psychotherapy because of the drug’s unpleasant side effects, which include dry mouth and dizziness.

“Our results demonstrate that both imipramine and cognitive-behavioral therapy [CBT] are better than pill placebo for treatment” of panic disorder, the researchers write in the journal report. “Imipramine produced a superior quality of response, but CBT was more durable and was somewhat better tolerated.”

Dr. Richard Glass, a Chicago psychiatrist and deputy editor of the Journal of the American Medical Association, says the study emphasizes the importance of viewing panic disorder as a treatable, chronic illness. “It hasn’t been as widely known as it should be,” says Glass, who wrote an editorial accompanying the journal article.

Panic attacks, which occur about twice as commonly in women as men, can mimic some of the symptoms of heart attack. As a result, many doctors may overlook the emotional disorder as a cause of chest symptoms and do nothing about it when they find that a patient isn’t having a heart episode, Glass says.

Similarly, many people who have panic attacks are unaware they have a wide range of treatment options, he says.

In addition to imipramine, which has been available for some two decades, newer antidepressants like Zoloft and Paxil also have been approved for treatment of panic disorder. These drugs are as effective as imipramine, Glass says, but have the advantage of not being fatal if taken in overdose amounts.

What To Do

“We know that these treatments work, but we don’t yet know which treatments work best for which people,” says Jerilyn Ross, a Washington, D.C., social worker and president of the Anxiety Disorders Association of America.

Ross, author of Triumph Over Fear (Bantam, 1994), says the worst thing a person with panic disorder can do is neglect it because the condition can lead to depression and substance abuse if unchecked.

Nor should patients who fail one therapy lose hope and think they’ll be luckless with others, she says.