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Guideline: The objective of continuation treatment is to decrease the likelihood of relapse (a return of the current episode of depression). If patients respond to acute phase medication, it is generally continued at the same dosage for 4 to 9 months after return to the clinically well state. (Strength of Evidence = A.)
The recommendation for continuation medication treatment rests on a few randomized controlled trials with medication in continuation phase treatment, a substantial number of open continuation trials, and a more substantial number of such trials in maintenance phase studies. In general, it is preferred that acute phase response to medication be followed by continuation treatment with the same medication at the same dosage. Early discontinuation is followed by a roughly 25 percent relapse rate within 2 months (Maj, Veltro, Pirozzi, et al., 1992; NIMH, 1985).
Unless maintenance treatment is planned, antidepressant medication is discontinued at 4 to 9 months or tapered over several weeks (TCAs should be tapered). Patients are followed during the next several months to ensure that a new depressive episode (recurrence) does not occur. If a major depressive episode does return after discontinuation of medication, the patient is likely to respond to the same medication at the same dosage effective previously, which should then be continued for 4 to 9 months; in other words, the depression should be treated as a new episode. Thereafter, discontinuation may be attempted unless the patient has become a candidate for maintenance treatment.
Guideline: A decision to implement continuation phase psychotherapy depends on the patient’s residual symptoms, psychosocial problems, history of psychological functioning between episodes, and the practitioner’s and patient’s judgment about the need for such treatment. Continuation psychotherapy can be added to continuation medication following acute phase response to either medication alone or the combination. (Strength of Evidence = C.)
No studies have evaluated acute response to medication followed by continuation phase psychotherapy or vice versa. In all cases, continuation phase treatment should be monitored for symptom breakthrough.
Continuation phase psychotherapy following acute treatment response to psychotherapy has not been studied in randomized controlled trials to date. Suggestive, albeit indirect, evidence for better, longer term outcome s available from two open continuation studies of cognitive therapy (Blackburn and Bishop, 1983; Jarrett, Ramanan, Eaves, et al., 1992) and one randomized controlled trial with interpersonal psychotherapy (Weissman, Prusoff, DiMascio, et al., 1979). Thus, there is only scant evidence to confirm or disconfirm the utility of continuation psychotherapy alone at once or twice a month for 6 to 8 months following acute treatment response.
Once the depressive symptoms have remitted with medication, therapy aimed at residual or persistent psychosocial problems is logical and reasonable. However, the efficacy of these types of intervention in this sequence has not been well studied. A notable exception is one controlled continuat~on/maintenance phase trial (32 weeks) of high versus lower contact with a focus on interpersonal function following response to acute phase medication alone (Weissman, Prusoff, DiMascio, et al., 1979). This study revealed that medication, but not placebo (with or without psychotherapy), prevented relapse/recurrence. This fmding suggests that acute phase medication responders should be continued on medication and not switched to psychotherapy alone as a continuation/maintenance treatment. On the other hand, psychotherapy as opposed to no psychotherapy was associated with better social adjustment 1 year later.
Continuation medication treatment is also used following acute response to ECT and generally reduces the relapse/recurrence rate. By extrapolation from medication trials, patients should be followed up for relapse/recurrence of the disorder and should be maintained on antidepressant medication for at least 8 months. However, in some patients who have not responded to trials of many medications, but respond to ECT as acute treatment, continuation ECT is a treatment option; some of these ECT-responsive, medication-resistant patients will also not respond to continuation medication (Sackeim, Prudic, and Devanand, 1990; Sackeim, Prudic, Devanand, et al., 1990). There are no randomized trials of continuation ECT, but case reports suggest a potential role for this treatment. Psychotherapy alone following acute phase ECT has not been studied; given the apparent prophylactic efficacy of medication and continuation ECT in particularly refractory patients, continuation phase psychotherapy alone following acute phase ECT is not recommended.
Guideline: Maintenance treatment is aimed at preventing a new episode of depression. Patients who have had three or more episodes of mayor depression are potential candidates for long-term maintenance antidepressant medication. Maintenance medications are generally of the same type and dosage found effective in acute phase treatment. (Strength of Evidence = A.) Maintenance psychotherapy does not appear to be effective in preventing a recurrence, although it may delay the onset of the next episode.(Strength of Evidence=B.)
Patients who had three episodes of major depression have a 90 percent chance of having another (NIMH, 1985). In fact, the World Health Organization (WHO) recommends considering maintenance treatment for patients who have experienced two depressive episodes within a 5-year period (Coppen, Mendelwics, and Kielholz, 1986). Clinical issues that affect the decision for instituting maintenance medication include:
Table 16 provides an overview of the considerations for maintenance medication based on the available maintenance phase studies, the NIMH Consensus Conference (NIMH, 1985) on maintenance treatment may vary from 1 year to a lifetime, depending on the patient's history (many, frequent episodes argue for longer periods); the likelihood of severe, precipitous recurrences; treatment side effects; and patient preference.
Table 16. Considerations for maintenance medication
| Considerations | Strength of indication |
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Very strongly recommended
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The practitioner and patient should discuss the pros and cons of maintenance treatment before embarking on it. A consultation with a psychopharmacologist may be particularly useful when maintenance treatment is under consideration.
The panel’s recommendations are based on the following considerations:
Based on the evidence that patients with a family history of recurrent major depressive or bipolar I or II disorder are more likely themselves to have recurrent major depressive disorder (Winokur, 1991; Winokur and Kadrmas, 1989; Winokur and Wesner, 1987), it is logical to consider those with two episodes of major depressive disorder and such a family history as potential candidates for maintenance medication. Earlier age at onset of the initial episode of major depressive disorder is associated with a greater familial incidence of the disorder (Strober, 1984; Strober and Carlson, 1982; Winokur, 1979), as well as an earlier and more likely recurrence once treatment has ended (Giles, Jarrett, Biggs, et al., 1989; Giles, Jarrett, Roffwarg, et al., 1987).
Maintenance psychotherapy (at least in once-a-month sessions) does not appear to be effective in ultimately preventing a recurrence, though it may delay by months the onset of the next episode (Frank, Kupfer, Perel, et al., 1990). The efficacy of more frequent maintenance psychotherapy has not been evaluated. For selected patients with recurrent depression, such as those undergoing surgery; those who are pregnant or trying to become pregnant; and those in athletic competitions or occupational roles that preclude medication for a fixed, limited time period, maintenance psychotherapy may have an important role if the patient has had a thorough acute and continuation phase response to medication plus psychotherapy.
Guideline: There is very strong evidence that specific medications prevent relapse/recurrence in most patients with recurrent forms of major depressive disorder. Since the episode onset date may not be readily determined, particularly in first-episode patients, most patients should receive the full therapeutic dosage of antidepressant drug for 4 to 9 months (the average duration of a major depressive episode) of continuation therapy after symptom remission is achieved. In those for whom the onset date is known, a somewhat shorter continuation phase may be attempted, but it should not be less than 4 months. For those with episodes of 2 years or more, it may be wise to pursue a continuation period of at least 9 months. Patients who have a recurrence shortly following continuation therapy withdrawal may require long-term maintenance medication. (Strength of Evidence = A.)
Several double-blind extension trials for those who responded to acute phase amitriptyline are consistent with the notion that extended medication exposure following response to acute phase treatment is associated with a low relapse or recurrence rate (e.g., Mendels, Amin, Chouinard, et al., 1983; Othmer, Othmer, Stern, et al., 1983). However, to be certain that such exposure is in fact specifically benefiting patients, randomized, controlled continuation or maintenance trials are essential. These trials engage patients who have responded to acute phase treatment, and who are then randomly assigned and treated under double-blind conditions either with the medication to which they responded or with pill placebo. The relapse rates (if randomization occurs prior to continuation phase) or recurrence rates (if randomization occurs after continuation phase) are then compared between placebo and medication.
Mindham, Howland, and Shepherd (1973) established that continuation treatment with either amitriptyline or imipramine for 6 months was more beneficial (22 percent relapsed) than placebo (50 percent relapsed) for acute phase responders to these medications. Similar results were reported by Stein’ Rickels, and Weise (1980), who randomly assigned acute phase amitriptyline responders to either amitriptyline (28 percent relapsed) or placebo (69 percent relapsed) for 6 months of continuation treatment.
In a randomized, double-blind controlled continuation maintenance trial reported in various publications (DiMascio, Klerman, Prusoff, 1975; Klerman, DiMascio, Weissman, et al., 1974; Paykel, DiMascio, Haskell, et al., 1975; Paykel, DiMascio, Klerman, et al., 1976), responders to acute phase amitriptyline (6 weeks) were randomly assigned to high- or lowcontact case management psychotherapy while continuing amitriptyline. Two months later, while continuing high or low contact psychotherapy, patients were randomly assigned to (a) continued amitriptyline, (b) pill placebo, or (c) no medication for the next 8 months (largely a maintenance trial). Results revealed relapse/recurrence rates of 12.2 percent (amitriptyline) versus 29.2 percent (placebo) versus 26.6 percent (no medication) over the next 8 months. Psychotherapy had no effect on the relapse/recurrence rate.
Glen, Johnson, and Shepherd (1984) reported the multisite Medical Research Council Study involving 136 patients who, having responded to acute phase medication (practitioner’s choice, median duration 8.5 weeks), were randomized to and treated under double-blind conditions for up to 3 years with lithium, amitriptyline, or placebo. Recurrence rates for amitriptyline were 30 percent (at 6 months postrandomization), 53 percent (at 12 months), 63 percent (at 24 months), and 69 percent (at 36 months). The corresponding rates for placebo were 66 percent, 67 percent, 78 percent, and 89 percent. Coppen, Ghose, Montgomery, et al. (1978) randomly assigned patients with major depression who responded to acute phase amitriptyline to either placebo or continued amitriptyline at the beginning of continuation treatment and followed them for 1 year. Again, a lower relapse/recurrence rate was associated with amitriptyline. Giller, Bialos, Harkness, et al. (1985) (see also Bialos, Giller, Jatlow, et al., 1982) randomly assigned outpatients with major depression who had recovered and been stabilized for at least 6 months to either continued amitriptyline or placebo. Eleven of 15 (73 percent) on placebo, compared with 1 of 9 (11 percent) on continued amitriptyline, had a recurrence within 1 year. Most patients in this study had been stable while in maintenance therapy for several years prior to the study.
For imipramine, double-blind extensions of acute phase treatment (from 6 to 12 weeks) also revealed that (1) those who responded by 6 weeks continued to respond to imipramine, and (2) some who partially responded by 6 weeks fully responded by 12 weeks (Liebowitz, Quitkin, Stewart, et al., 1988; Mann, Georgotas, Newton, et al., 1981; Peselow, Filippi, Goodnick, et al., 1989a,b; Quitkin, Stewart, McGrath, et al., 1988).
In a randomized, placebo-controlled double-blind 2-year maintenance trial, Prien, Klett, and Caffey (1973) found a distinct and significant advantage of imipramine over placebo for recurrent depression. Recurrence rate was 29 percent for imipramine versus 85 percent for placebo.
Randomized, double-blind placebo-controlled maintenance trials in mixed samples (bipolar plus unipolar, recurrent major depressive disorders) (Kane, Quitkin, Rifkin, et al., 1982; Prien, Kupfer, Mansky, et al., 1984) or bipolar patients only (Shapiro, Quitkin, and Fleiss, 1989) revealed similar prophylactic effects for imipramine as for amitriptyline. For example, in the unipolar group, Prien, Kupfer, Mansky, et al. (1984) found that 55 percent remained well after both 1 and 2 years of maintenance imipramine, compared with 30 percent and 25 percent, respectively, for placebo.
In the most definitive maintenance study to date (Frank, Kupfer, Perel, et al., 1990), a 22.6 percent recurrence rate was found for imipramine, compared with 78.2 percent for placebo over 3 years. Those in maintenance psychotherapy (with or without a placebo) suffered a 44.2 percent recurrence rate over the same period. The advantage of prolonged maintenance medication was recently reported for the same cohort after 5 years (Kupfer, Frank, Perel, et al., 1992). However, caution is warranted, because the type of acute treatment to which patients initially respond may dictate the relative efficacy of different maintenance treatments (Greenhouse, Stangl, Kupfer, et al., 1991).
Several open-label continuation/maintenance phase studies of fluoxetine in major depressive disorder in adult or geriatric patients suggest long-term efficacy (Cohn and Wilcox, 1985; Feighner, 1984; Rickels, Smith, Glaudin, et al., 1985). One randomized, double-blind placebocontrolled maintenance phase trial was conducted over a 1-year period on 222 psychiatric outpatients with major depressive disorder and compared fluoxetine to placebo (Montgomery, Dufour, Brion, et al., 1988). All patients had initially responded to a 6-week open trial with fluoxetine during acute phase treatment, and all were symptom-free for 4 to 5 months (continuation phase) prior to randomization for this maintenance study. All patients had had at least two episodes of major depression in the 5 years preceding this study. One hundred eighty-two completed the 1-year maintenance trial or developed a recurrence. On fluoxetine, 26 percent had a recurrence, compared to 57 percent on placebo—a significant difference. In a recent placebo-controlled, randomized study of sertraline for 44 weeks following acute phase response, placebo was associated with a 45.7 percent relapse/recurrence rate, compared to 13.0 percent for sertraline (Doogan and Caillard, 1992). Similar results are suggested for paroxetine (Montgomery and Dunbar, 1991).
The only randomized, placebo-controlled maintenance study in adults of an MAOI (phenelzine) found that phenelzine (at 45 or 60 mg/day) was associates with a much lower recureence rate (30percent) than placebo (over 80 percent) in the first 12 months of maintenance (Robinson, Lerfald, Bennett, et al., 1991). A similarly robust maintenance effect with phenelzine was found in a randomized, double-blind placebo-controlled maintenance trial in geriatric patients (Georgotas, MCcue, and Cooper, 1989).
Other extension studies of acute phase treatment without placebo controls reveal similar findings for maprotiline (coopen, Montgomery, Gupta, et al., 1976), doxepin (Feighner and Cohn 1985), bupropion (Mendels, Amin, Chouinard, et al., 1983; othmer, othmer, Preskorn, et al., 1988), and trazodone (Fabre and Feighner, 1983; Feighner, 1984; Mann Georgotas, Newton, et al., 1981). No randomized continuation/maintenance phase studies for amoxapine, fluvoxamine, desipramine, doxepin, isocarboxazid, protriptyline, tranylcypromine, or trimipramine were found.
In summary, strong evidence supports the use of specific medications to prevent relapse/recurrence in most patients with recurrent forms of major depressive disorder. Whether this efficacy extends to unstudies antidepressants is an open question, though logic and basic pharmacologic principles suggest that it does. Whether some patients (and which ones) can forgo maintenance treatment after 2 to 3 years is unstudies. If the practitioner attempts to discontinue maintenance treatment, the patient should be monitored closely for the initial 6 to 12 months following discontinuation of the medication
Guideline: Patients who have responde fully in the acute phase of treatment need to be seen only once every 1 to 3 months during the continuation and maintenance phases to evaluate symptoms, efficacy, and side effects and to promote adherence. (Strength of Evidence = B.)
If there is significant symptom breakthough, the patient should be seen more quickly and monitored more frequently so that timely action can be taken. Early treatment of new episodes reduces the overall time that the patient is ill (Kupfer, Frank, McEachran, et al., 1990)
Guideline: During both the continuation and maintenance phases of treatment, the medication dosage should be maintained at the full dosage initially required to attain symptom remission in the acute phase treatment. (Strength of Evidence = B)
A maintenance therapy trial (Frank, Kupfer, Perel et al., 1990) showed a comparatively lower recurrence rate for patients taking imipramine at the full acute phase dosage than for those taking the lower maintenance dosage used in previous studies (Prien, Balter, and Caffey, 1978).
There is no need to check blood levels routinely during continuation or maintenance treatment. However, blood level determinations for those antidepressants whose minimal and/or maximum therapeutic levels are known may be needed if patients develop a toxic reaction or if the depressive episode recurs. For patients who develop another nonpsychiatric medical disorder requiring medication(s) that modify antidepressant levels, blood level determinations may also be helpful.
Ten to 20 percent of patients report that some depressive symptoms return during continuation or maintenance treatment. This symptom breakthrough is often brief, mild and self-limited. Support and obeservation are indicated. If the breakthrough is severe or prolonged, action is indicated. In some cases, symptoms may result from a change in antidepressant blood level due to induction of metabolic enzymes. If this cause is suspected, a blood level determination may be informative for medications whose lower therapeutic and toxic levels are known. Alternatively, daily doses can be increased empirically until symptom remission is again achieved. Caution is necessary, however, because symptom breakthrough may be associated with blood levels in the toxic range and some patients do not show marked side effects at these levels. The adjusted dosage is then continued until drug treatment is discontinued. Increased side effects during symptom breakthrough may be a clinical clue to an excessive drug level.
In some patients, symptom breakthrough is the result of the inability of the current medication to suppress symptoms. If dosage adjustment fails, consultation, augmentation, or alternative medications should be considered.
Guideline: Antidepressant medications are generally safe, even with long-term use. However, medications should be discontinued if they are not required. All patients with a single episode of major depressive disorder are advised to discontinue medication after 4 to 9 months of continuation treatment since only 50 percent will have another episode of major depressive disorder. Even then, the next episode may be years hence. Whenever possible, the decision to discontinue treatment is made collaboratively with the full participation and knowledge of the patient. If the full depressive episode recurs during or shortly after discontinuation, the episode has not “run its course,” and the full therapeutic dosage is typically reinstated. (Strength of Evidence = A.)
If a patient is reluctant to discontinue medication, it may be continued for another 3 to 6 months. However, a discussion of the basis for this reluctance is indicated.
Guideline: It is advisable to taper all TCAs on discontinuation if the patient has had exposure at therapeutic dosages for 3 months or more. A tapering schedule over 2 to 4 weeks is usually well tolerated. (Strength of Evidence = A.)
Rapid discontinuation of medication can result in insomnia, aches and pains, and nausea. Patients should be warned to expect transient sleep disturbance during medication tapering. A recent report suggests that, for imipramine, a more abrupt discontinuation is associated with a higher recurrence rate than is a more gradual schedule (Greenhouse, Stangl, Kupfer, et al., 1991). Thus, tapering over 6 to 8 weeks is also an option. It is unclear whether it is necessary to taper maprotiline and amoxapine.
Guideline: There is no evidence that bupropion, MAOIs, fluoxetine, paroxetine, sertraline, or trazedone must be tapered. (Strength of Evidence = B.)
If anxiolytics or sedative hypnotics have been used, they should be tapered to avoid rebound anxiety/insomnia. (These medications should generally not be used for more than 12 weeks of treatment, because their efficacy has not been established beyond this time frame. Furthermore, anxiolytics and sedative hypnotics are usually not required as adjuncts to standard antidepressants.)
If the major depressive episode recurs during or shortly after discontinuation, the depressive episode has not “run its course,” and the full therapeutic dosage should be reinstated. Clinician or self-report symptom severity measures may provide a rapid, objective evaluation that makes it possible to determine whether the syndrome is actually returning or the patient is only experiencing transient anxiety/worry. Some patients manifest a transient mild return of some symptoms during tapered discontinuation. If this occurs, the speed of tapering should be slowed, but it may be continued.
Once tapered off medication, patients should be encouraged to monitor their symptoms. (Some practitioners provide patients with self-report scales to be completed monthly and mailed back for followup.) Persons who develop a new episode are most likely to do so within 8 months following discontinuation (Prien and Kupfer, 1986). Early treatment, if the full syndrome returns, should include the same treatment to which the patient previously responded. Early intervention reduces the length of the episode (Kupfer, Frank, and Perel, 1989).
Guideline: Continuation psychotherapy to improve psychosocial functioning may be added to the treatment regimen for those who respond to acute phase medication. (Strength of Evidence = C.) Maintenance psychotherapy as the sole treatment to prevent recurrence is generally not recommended unless the patient, for some reason (e.g., pregnancy), needs to avoid medication. (Strength of Evidence = B.)
The objective of continuation psychotherapy is the same as that for medication—to maintain the patient in an asymptomatic state. The efficacy of continuation psychotherapy alone as a treatment is not well established.
There are no randomized controlled trials of continuation or maintenance phase cognitive therapy. Indirect evidence from a few studies suggests that some patients who respond to cognitive therapy in the acute phase of treatment may continue to reap a prophylactic benefit once acute phase cognitive therapy is stopped, compared to those treated with only antidepressant medication in the acute phase.
In a recent study of cognitive therapy as an adjunct to pharmacotherapy, Miller and colleagues (1989) determined that patients given standard treatment (i.e., hospital milieu and pharmacotherapy), or cognitive therapy plus standard treatment, or social skills training plus standard treatment did not differ in acute symptom reduction after 3 weeks of hospitalization. After an additional 20 weeks of outpatient continuation treatment, however, both cognitive therapy plus standard treatment and social skills training plus standard treatment reduced self-reported depressive symptoms more than did medication plus clinical management alone effects that were maintained at 6- and 12-month followup. By the end of outpatient treatment, patients with higher levels of cognitive distortion had responded better to cognitive therapy plus standard treatment or to social skills training plus standard treatment than to standard treatment alone. Conversely, persons with lower levels of cognitive distortion showed no preferential response. These few findings provide a very tentative basis to consider continuation cognitive therapy or other psychotherapies for those with residual symptoms after acute phase treatment, especially if they are cognitive in nature.
Some evidence suggests that continuation cognitive therapy in responders is beneficial compared to no continuation cognitive therapy. The relapse/recurrence rate following acute phase cognitive therapy in responders is on the order of 40 to 60 percent, based on naturalistic follow up studies (Beck, Hollon, Young, et al., 1985; Covi and Lipman, 1987; Gallagher and Thompson, 1982; Gallagher-Thompson, HanleyPeterson, and Thompson, 1990; Kovacs, Rush, Beck, et al., 1981; O’Leary and Beach, 1990; Ross and Scott, 1985; Shea, Elkin, Imber, et al., 1992). In contrast, only a 23 percent relapse rate was detected at 1-year follow up for cognitive therapy responders who received 8 months of continuation cognitive therapy (Blackburn, Eunson, and Bishop, 1986). Similarly, the relapse rate was 19 percent in cognitive therapy responders given biweekly to monthly continuation cognitive therapy over 8 months, compared to a 44 percent relapse rate for those (in a separate trial) who received only acute phase cognitive therapy (Jarrett, Ramanan, Eaves, et al., 1992). While both reports suggest that continuation cognitive therapy may help to sustain the response to acute phase cognitive therapy, both are open trials without randomized comparison groups. Only a true randomized continuation/maintenance trial following acute phase response to cognitive therapy versus a control condition can determine whether continuation/maintenance cognitive therapy is effective.
No randomized controlled or open trials have been performed for either continuation or maintenance phase behavioral therapy.
Two studies of continuation/maintenance phase interpersonal psychotherapy are available. The first revealed that interpersonal psychotherapy (acute/continuation phase) resulted in better social/ occupational/marital adjustment 1 year later than did no interpersonal psychotherapy, but the followup was naturalistic (Klerman, DiMascio, Weissman, et al., 1974). The second showed that maintenance interpersonal psychotherapy alone delayed, but did not ultimately prevent, a new recurrence in outpatients with highly recurrent major depressive disorder, who responded during the acute phase of treatment to the combination of imipramine plus interpersonal psychotherapy and who sustained the well state for 16 weeks of combined continuation phase treatment (Frank, Kupfer, Perel, et al., 1990).
No randomized controlled or open trials have been undertaken for either continuation or maintenance phase marital therapy.
There are no randomized controlled or open trials of either continuation or maintenance phase brief dynamic psychotherapy.
Maintenance psychotherapy as the sole treatment to prevent recurrence of major depressive disorder is generally not recommended for two reasons. First, for those who have one or two episodes, maintenance treatment is usually not indicated. Second, for those who have had three or more episodes, maintenance medication has established efficacy, but maintenance psychotherapy alone (without medication) is less effective at preventing the next episode (Frank, Kupfer, Perel, et al., 1990; Weissman, Prusoff, DiMascio, et al., 1979). In selected clinical situations, such as during pregnancy, efforts to become pregnant, or times during which occupational demands require patients to take no medication, maintenance psychotherapy may be used for a limited time in an attempt to maintain a medication- and symptom-free state.
Given the strong evidence for prophylaxis against a new episode in patients taking medication, the few studies of psychotherapy, and the relatively disappointing prophylactic effects of maintenance psychotherapy in these studies, medication is the essential, if not the only needed, treatment to maintain symptomatic remission in highly recurrent depressions. However, evidence from some studies suggests a broader domain of improvement if medication and psychotherapy are combined for acute phase treatment (Klerman, DiMascio, Weissman, et al., 1974; Weissman, Klerman, Prusoff, et al., 1981). By logical extension, similar findings may be expected for continuation phase combined treatment in some patients.
The optimal length of therapy used as an adjunct to medication to resolve associated psychosocial problems has not been established. In practice, it is typically determined individually, based on resolution of these associated problems. The only formal study of continuation interpersonal psychotherapy used up to 16 sessions, once patients had symptomatically responded to acute treatment with medication over 8 weeks (Weissman, Prusoff, DiMascio, et al., 1979).
Research on the optimal frequency of continuation or maintenance phase psychotherapy visits is lacking. The patient in continuation phase psychotherapy alone usually contracts with the therapist for followup visits at a frequency indicated by the type of psychotherapy and the degree of need (usually one to three times each month). The practitioner should continue to be available to the patient after acute phase treatment, if the symptoms return. If the patient is in the continuation or maintenance phase of treatment and is receiving psychotherapy along with medication, psychotherapy visits may be needed weekly for up to 20 sessions. Once therapy is discontinued, the prescribing physician should still see the patient at least once every 2 to 3 months to evaluate symptoms, reinforce adherence, and check medication side effects until the medication is discontinued.
Guideline: It is important to inform patients that symptoms may recur during continuation/maintenance treatment and that the practitioner should be informed of them. (Strength of Evidence = A.)
Some patients will feel that they have failed and drop out of treatment if symptoms return. The practitioner should anticipate this tendency and educate the patient before continuation or maintenance phase treatment is begun. In the event of symptom breakthrough during continuation phase psychotherapy alone, the practitioner must distinguish between transient mild symptoms and a full relapse. For mild transient symptoms, the number of therapy visits may be increased in an attempt to resolve these symptoms. It is essential that the patient be informed both at the onset (when selecting acute treatment) and at the time of any significant symptom breakthrough that medications are potentially effective options. If the symptoms are more severe, persistent, disabling, or if the patient requests it, acute phase treatment with medication should be strongly considered.
Continuation phase combined treatment is not uncommon practice, especially for patients with the more chronic or complex forms of depression that are often seen in tertiary care settings. The rationale for combined continuation treatment is to maintain symptom remission and to improve psychosocial function. It is unclear which patients specifically benefit from this combination. The general principles outlined for continuation or maintenance management with either medication or psychotherapy hold for combined treatment.
Guideline: Assuming a full response to combined treatment in acute or continuation phases, the evidence shows that medication alone may be all that is necessary to prevent a recurrence. A substantial number of clinicians believe that some patients will benefit from targeted psychotherapies in continuation or maintenance phases if only partial symptomatic response or psychosocial restoration was obtained with medication alone. (Strength of Evidence = B.)
In an open trial of interpersonal psychotherapy combined with imipramine, 8.5 to 15.3 percent of patients relapsed during continuation phase treatment (Frank and Kupfer, 1987). One study found that patients who responded to acute phase medication alone showed improved, longer term psychosocial adjustment when interpersonal psychotherapy was included in continuation treatment (Klerman, DiMascio, Weissman, et al., 1974). However, in a randomized controlled maintenance trial of combined treatment, the prevention of recurrences obtained could be accounted for by medication (Frank, Kupfer, Perel, et al., 1990). That is, combined treatment did not add to the prophylaxis attained by medication alone.
Since maintenance medication without formal psychotherapy leads to sustained symptom remission for many patients in the maintenance phase, both those responding in the acute phase to medication alone (Klerman, DiMascio, Weissman, et al., 1974; Weissman, Klerman, Prusoff, et al., 1981) and those responding in the acute phase to combined treatment (Frank, Kupfer, Perel, et al., 1990), continuation and maintenance medication is the mainstay of prophylaxis for recurrent forms of major depressive disorder. Whether psychotherapy meaningfully adds to the prophylaxis found with continuation medication is unknown. Many practitioners believe psychotherapy is helpful in symptomatically unstable patients and helps to prevent relapse, especially in those with associated personality disorders or those with a previously chronic or complex course.
It is also unknown whether combined maintenance treatment with medication and psychotherapy helps similar, particularly problematic patients. The one maintenance randomized controlled trial that tested combined treatment excluded patients who had partial or poor interepisode recoveries from the recurrently depressed sample (Frank, Kupfer, Perel, et al., 1990).
Principles for discontinuing medication are as described earlier.
The primary care practitioner may wish to obtain a second opinion from a psychiatrist or other mental health care professional regarding one or more of the following:
In general, the more specific the question(s), the more useful the consultation will be. The major difficulties in obtaining the consultation are:
It is optimal to establish a working relationshiop with one or more such professionals, who should make themselves easily and readily available to the primary care provider. Several medical schools now offer consultation by telephone to primary care providers who may be in geogrphically remote locations.
Many cases of major depressive disorder can be effectively treated in primary care settings, especially if diligent attention is paid to symptom assessment, dosage adjustment, psychosocial disabilities, and adherence. As with the treatment of hypertension, diabetes, hypercholesterolemia, and most other medical conditions, treatment of depression aims at optimal regulation of the disorder—not simply improvement. Acceptance of a partial response when full symptomatic remission and restoration of psychosocial function are possible may lead to greater chronicity, difficulty in subsequent treatment, and disability from or difficulties in managing associated general medical disorders, as well as unneeded pain and suffering. The practitioner is strongly encouraged to aim for full remission and not to delay consultation inappropriately in those who are not remitting.
Persuading a patient to see a consultant can be difficult. This goal can be facilitated by providing patients and families with information about depression and by reassuring them that most consultations require only one or two visits, that most do not require inpatient treatment, and that the more severe forms of depression are medical conditions for which a wide range of treatments are available.
The practitioner should inform patients and families that they may request a second opinion at any time and that the practitioner, while beginning treatment, may later ask for a second opinion as well. Bringing up the possibility of consultation early (though many patients will not require it) can often avoid the patient’s later rejection of the consultation, as it is then seen as part of a larger treatment plan. This strategy also reduces the demand that these patients, should they fail to respond fully, can make on primary care providers. Since the treatment of depression is rapidly changing, special expertise for selected cases can save patients time, money, and suffering.
It is important that mental health care professionals be readily available (same day or next day) to provide an optimal consultation or second opinion to busy primary care providers. Too often, mental health care professionals leave primary care providers to cope with depressed patients for weeks prior to consultation. This experience frustrates practitioners, unnecessarily delays treatment, and causes patients unneeded anxiety and suffering.
Mental health care professionals should outline specific options or steps for the primary care provider and should provide patients with the same information. The mental health care professional often wants to obtain a history from both the patient and a friend or family member. The primary care provider should alert the patient to that possibility. Patients may themselves have questions in addition to those already raised with the primary care provider. Patients and families should be encouraged to raise those questions with both primary care providers and consultants. Finally, mental health care professionals should provide a rapid oral response and a brief written response to the primary care provider and should be open to subsequent patient visits, if needed.
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