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Chapter 3

Course and Prognosis

Depression as a Clinical Entity

In Chapter 2, depression was treated as a psychopathological dimension or syndrome. The clinical features of depression were examined in cross-section, that is, in terms of the cluster of pathological phenomena exhibited at a given point in time. In this chapter, depression is treated as a discrete clinical entity (such as bipolar disorder or dysthymia) that has certain specific characteristics occurring over time in terms of onset, remission, and recurrence. As a clinical entity or reaction type, depression has many salient characteristics that distinguish it from other clinical types such as schizophrenia, even though these other types may have depressive elements associated with them. The depressive constellation as a concomitant of other nosological entities will not be described in this chapter but will be considered later in terms of its association with schizophrenic symptomatology in the schizoaffective category (Chapter 8).

Among the important characteristics of the clinical entity of depression are the following: There is generally a well-defined onset, a progression in the severity of the symptoms until the condition bottoms out, and then a steady regression (improvement) of the symptoms until the episode is over; the remissions are spontaneous; there is a tendency toward recurrence; the intervals between attacks are free of depressive symptoms.

Importance of Course and Outcome

The longitudinal aspects of depression have been the subject of many investigations since the time of Kraepelin. Adequate information regarding the short-term and long-term course of depression is important, not only for practical management, but also for an understanding of the psychopathology and for evaluation of specific forms of treatment. Considerable data on the life histories of depressed patients were accumulated before the advent of the specific therapeutic agents—psychological treatments (such as cognitive and interpersonal therapy), electroconvulsive therapy (ECT), and drugs. These data are generally regarded as reflecting the natural history of the disorder, although it is difficult to separate out the effects of hospitalization.

The physician charged with making a determination of the prognosis in a given case is confronted with a number of questions.

1. In the case of a first episode of depression, what are the prospects for complete remission, and what is the likelihood of residual symptoms or of a chronic, unrecovered state?

2. What is the probable duration of the first attack?

3. What is the likelihood of recurrence, and what is the probable duration of any multiple attacks?

4. How long must one wait following a patient’s remission from a given attack before ruling out the likelihood of recurrence?

5. What is the risk of death through suicide?

Answers to these questions can be provided by reference to research on early cases diagnosed as manic-depressive psychoses and subsequent studies that elaborated the prior findings. A number of fairly well-designed studies have been conducted to determine the fate of such patients. It should be emphasized that much of the available data applies primarily to hospitalized patients.

A series described by Paskind as “manic depressive” in 1930 undoubtedly contained a preponderance of cases that would later be diagnosed as “neurotic-depressive reactions.” Since this study antedated the modern somatic therapies, the findings may be assumed to be relevant to the natural history of neurotic-depressive reactions.

Systematic Studies

Kraepelin¹ studied the general course of 899 cases of manic-depressive psychosis. The period of observation varied considerably; some patients were followed for brief periods and others for as long as 40 years. Moreover, since the follow-up depended largely on readmission to the hospital, the information on patients who were not readmitted is scanty. Despite these limitations, his study is of great value in providing solid facts regarding recurrent episodes, frequency and duration of the attacks, and duration of the intervals between attacks. His sample was as follows: single depression, 263; recurrent depression, 177; biphasic single episode, 106; combined, recurrent, 214; single manic episode, 102; recurrent manic, 47. Biphasic was used for cases in which both manic and depressive episodes occurred. These have been designated by terms such as compound, mixed, combined, double-form, cyclothymic, and cyclical. Alternating and circular refer to cases in which one phase follows immediately after the opposite without any free interval. “Closed circular type” refers to uninterrupted manic and depressive cycles.

Paskind’s study^2,3,4 of cases of depression seen in private practice provides data on the course of depressions observed outside the hospital. Although there are many serious methodological deficiencies in this study, the data presented are relevant to milder episodes of depression. Paskind reviewed the records of 633 cases of depression in the private practice of Dr. Q. T. Patrick. Although all of these cases had been placed in the all-inclusive category of manic-depressive psychosis, a review of the case histories presented in the articles leaves little doubt that these cases are actually descriptive of the bipolar mood disorders rather than psychosis. In reviewing the tabulated data presented by the author, it is apparent that his findings are based on 248 cases abstracted from the original group. The cases were collected over a period of 32 years, but there is no mention of the average period of observation or of any systematic attempt to obtain follow-up material on these patients. Paskind noted that 88 cases (32 percent) could be classified as “brief attacks of manic-depressive psychosis,” since the average duration of the episodes ranged from a few hours to a few days.

Paskind described the symptoms of the short attacks as exactly like those of longer attacks: profound sadness and unhappiness without obvious cause; self-reproach; self-blame; self-derogation; lack of initiative; lack of response to usual interests accompanied by keen awareness of this lack; avoidance of friends; a feeling of hopelessness; death wishes; and inclinations or desire to commit suicide. Paskind stated that the well-known antidotes for depression, such as a philosophic outlook, company of friends, amusements, diversions, rest, change of scene, and good news did not cause the attacks to disappear. “Instead one finds a person in a normal mood who without apparent cause becomes within a brief period profoundly sad and unhappy; in spite of all attempts to cheer him, the attack remains for from a few hours to a few days; when it does disappear it does so as abruptly and mysteriously as it came.”

Rennie⁵ did a follow-up study of 208 patients with manic-depressive reactions admitted to the Henry Phipps Psychiatric Clinic between 1913 and 1916. Atypical cases were not included because the author wanted to study only clear-cut manic-depressive (bipolar) reactions. Several patients having what seemed to be manic excitements at the time of admission developed schizophrenic reactions on long-term observation. These cases were excluded, as were cases of depression that had lost the preponderant depressive affect and had, in the course of years, evolved slowly into more automatic and schizophrenic-like behavior. Also excluded were depressive patients with hypochondriasis who had lost most of their depressive affect and who had sunk into a state of chronic invalidism with little depressive content. The material, consequently, can be regarded as following reasonably stringent criteria for diagnosing the manic-depressive syndrome.

Follow-up on these patients was obtained by letter, social service interview, physician’s interview, newspaper notices of suicide, and records from other hospitals. In only one case were no follow-up data obtained. The follow-up period evidently ranged from 35 to 39 years.

In Rennie’s study, the following clinical groups were described in order of frequency: (1) recurrent depression: 102 patients—15 had symptom-free intervals of at least 20 years between attacks, and 52 had remissions of at least 10 years; (2) Cyclothymic (biphasic), 49 patients in whom all combinations were observed, with elation and depression sometimes following each other in closed cycles; (3) single attacks of depression, recovered—26 patients; (4) single attacks of depression, unrecovered—14 patients, of whom 9 committed suicide; (5) recurrent manic attacks, 14 cases; (6) single manic attacks—two patients (These remained well for over 20 years after the attack. A third patient became manic for the first time at age 40 and was still hospitalized at age 64.)

A comparison of the relative frequency of depressed, biphasic, and manic patients observed in various studies is presented in Chapter 6.

Lundquist⁶ conducted a longitudinal study of 319 manic-depressive patients whose first hospitalization for this disorder was at the Langbrö Hospital in 1912–31. The investigator reviewed the records and checked the appropriateness of the diagnoses to “satisfy all reasonable demands in regard to reliability.” His sample consisted of 123 men (38 percent) and 196 women (62 percent).

After locating the discharged patients, follow-up was conducted by a personal examination of patients at the hospital, a home visit by a social worker if patients lived in Stockholm, a detailed questionnaire mailed to patients living outside of Stockholm, and a review of the hospital record of patients currently hospitalized elsewhere.

The period of observation varied considerably: 20–30 years, 42 percent; 10–20 years, 38 percent; less than 10 years, 20 percent.

The duration of an episode was defined as the time that elapsed between patients’ recognition of their symptoms and their return to their former occupation. Remission was based on a rough gauge of patients’ ability to resume their work and ordinary mode of life.

Onset of Episodes

The relative frequency of an insidious onset, as compared with an acute onset, was studied by Hopkinson⁷ for 100 consecutive inpatients diagnosed as having an affective illness. All were more than 50 years of age on admission, and 39 had suffered previous attacks before age 50; 80 patients were examined personally by the author, and in the remaining 20 cases, the pertinent data were abstracted from the case histories.

When the onset of the illness was studied, it was found that 26 percent of the cases exhibited a well-defined prodromal period; the remaining 74 percent of the cases were considered of acute onset. Complaints made by these patients in the prodromal period were vague and nonspecific. Tension and anxiety occurred in all to some extent. The duration of the prodromal period before the onset of a clear-cut depressive psychosis ranged from 8 months to 10 years; the mean duration was 33.5 months.

In a later study,⁸ Hopkinson investigated the prodromal phase in 43 younger patients (ages 16–48). Thirteen (30.2 percent) showed a prodromal phase of 2 months to 7 years (mean = 23 months). The clinical features of the prodromal period were chiefly tension, anxiety, and indecision.

In summary, 70–75 percent of the patients in both studies with an affective disorder had an acute onset.

The relationship of acuteness of onset to prognosis has been studied by several investigators, with contradictory results. Steen⁹ found, in a study of 493 patients, that the remission rate was higher among manic depressives who showed an acute onset than among those with a protracted onset. On the other hand, Strecker et al.,¹⁰ in a comparison of 50 recovered and 50 nonrecovered manic depressives, found that an acute onset occurred no more frequently in the recovered than in the chronic group. In a study of 96 cases grossly diagnosed as manic depressive, Astrup et al.¹¹ found that an acute onset favored remission.

Hopkinson⁸ found a significantly higher frequency of attacks per patient among his cases with an acute onset (mean = 2.8) than among those patients with a prodromal phase (mean = 1.3).

Lundquist⁶ reported that patients over 30 with an acute onset (less than a month) had a significantly shorter duration of their episodes than those with a gradual onset. In the age group of 30–39 years, the mean duration of the acute onset cases was 5.1 months and of the gradual onset cases, 27.2 months.

The average age of onset of depression varied so widely among these earlier studies that no definite conclusions could be drawn. The following statistics for the decade of peak incidence may serve as a rough guide: 20–30, Kraepelin¹; 30–39, Stenstedt,¹² Cassidy et al.,¹³ Ayd¹⁴; 45–55, Rennie⁵; 50 and older, Lundquist.⁶

Remission and Chronicity

There was considerable variation among the authors on the proportion of patients remaining chronically ill following the onset of depressive illness. It is difficult to make comparisons among the various studies because different diagnostic criteria were used, the definition of chronicity varied, the periods of observation varied, and in many studies, no distinction was made between those who became chronic after the first attack and those who became chronic only after multiple attacks.

The relatively well-designed retrospective study by Rennie indicated that approximately 3 percent were found on long-term follow-up to be chronically ill. Kraepelin reported that 5 percent of his cases became chronic. Lundquist reported that 79.6 percent of the depressives recovered completely from the first attack. Age of onset was a factor: the remission rate ranged from 92 percent for patients less than 30 years old to 75 percent in the 30–40 age group. It is probable that his percentages are lower than those of the others because of his more stringent definition of complete remission.

Astrup et al.¹¹ divided their group of manic-depressive patients into the categories of “chronic,” “improved,” and “recovered.” Of the 70 “pure” manic depressives, 6 (8.6 percent) were still chronically ill at the time of follow-up. The majority had recovered completely, and a minority showed residual “instability” and were classified as improved. (Precise figures for the improved and recovered categories are not available because of the lumping together of manic-depressive and schizoaffective patients.) The follow-up period was five years or more.

It is noteworthy that a patient may have an initial manic or depressive episode from which she or he recovers completely and, after a long symptom-free interval, may relapse into a chronic state. Rennie reported the case of a patient who had an initial episode of mania followed by depression, the entire cycle lasting about a year. He was symptom-free for 23 years afterward and then lapsed into a state of manic excitement lasting 22 years.

Kraepelin¹ indicated that a patient may have chronic depression of many years’ duration and still have a complete remission. He presented an illustrative case (p. 143) with a single attack lasting 15 years, from which the patient had made a complete remission.

Remission from Dysthymic Disorder

More recently, study of chronic, low-grade depression—referred to as “dysthymic disorder”—was reported by Klein et al.¹⁵ The diagnostic criteria for dysthymic disorder are listed in Table 3-1. (More detailed information on the classification of the various mood disorders is provided in Chapter 4.)

To study recovery in dysthymic disorder, Klein et al.¹⁵ used a prospective design and a naturalistic 5-year follow-up. Participants were 86 outpatients with early-onset dysthymic disorder, and 39 outpatients with episodic major depressive disorder. Follow-ups were conducted at 30 and 60 months. Only about half (52.9 percent) of the patients with dysthymic disorder had recovered after five years. Over an average of 23 months of observation, the relapse rate for this disorder was 45.2 percent.

Klein compared patients with dysthymic disorder and those with episodic major depressive disorder. The former spent 70 percent of the time over the 5-year follow-up meeting the criteria for a mood disorder; the latter spent less than 25 percent of the time meeting mood disorder criteria.

TABLE 3-1. Diagnostic Criteria for Dysthymic Disorder

A)	Depressed mood for most of the day, for more days than not, as indicated by subjective account or observation by others, for at least 2 years. Note: In children and adolescents, mood can be irritable and duration must be at least 1 year.
B)	Presence, while depressed, of two (or more) of the following:
	(1) poor appetite or overeating (2) insomnia or hypersomnia (3) low energy or fatigue (4) low self-esteem (5) poor concentration or difficulty making decisions (6) feelings of hopelessness
C)	During the 2-year period (1 year for children or adolescents) of the disturbance, the person has never been without the symptoms in Criteria A and B for more than 2 months at a time.
D)	No Major Depressive Episode has been present during the first 2 years of the disturbance (1 year for children and adolescents); i.e., the disturbance is not better accounted for by chronic Major Depressive Disorder, or Major Depressive Disorder, in Partial Remission.
E)	There has never been a Manic Episode, Mixed Episode or Hypomanic Episode, and criteria have never been met for Cyclothymic Disorder.
F)	The disturbance does not occur exclusively during the course of a chronic Psychotic Disorder, such as Schizophrenia or Delusional Disorder.
G)	The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism).
H)	The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Those with dysthymia had more symptoms, lower functioning, and higher probability of attempting suicide and being hospitalized than those with major depressive disorder. By the end of the 5-year follow-up, 94.2 percent (81 of 86) of the dysthymic disorder group had at least one lifetime major depressive episode. This figure includes the 77.9 percent (67 of 86) of this group who had already experienced superimposed major depression at the onset of the study. Among those patients with dysthymic disorder who had not reported a major depressive episode before the study (19 of 86), the estimated risk of having a first lifetime major depressive episode was 76.9 percent (14 of 19). Overall, these findings suggest that dysthymic disorder is a chronic, severe condition with a high risk of relapse.¹⁵

Remission from Functional Impairments

Buist-Bouwman et al.¹⁶ addressed the question of whether people who remit from a major depressive episode also recover from functional impairments. These impairments were assessed by the Short-Form-36 Health Survey and included things like physical functioning, vitality, pain, social functioning, and general health.

The study used data from the Netherlands Mental Health Survey and Incidence Study, and depression was diagnosed using the hierarchical rules of DSM-III-R. Those who suffered major depressive episodes during the course of psychotic or bipolar disorders were excluded. A total of 165 people were included in the study.

Results showed that 60 to 85 percent of the respondents did better or showed no change in functioning after recovery from depression, compared to their functioning prior to depression. Still, the average levels of functioning after depression were lower compared to people from a nondepressed sample, people who had never been depressed. Those who suffered from substance abuse and anxiety disorders, physical illness, and low social support showed poorer functioning. The authors suggested that a limitation of the study was that nonprofessional interviewers were used to determine the diagnosis of depression by structured interviews, and functioning was obtained by self-report.

Duration

Some idea of the average or expected duration of an episode of depression is obviously important so that the physician can adequately prepare the patient and family psychologically and give them a basis for making decisions about the business affairs of the patient as well as appropriate financial arrangements for his or her care.

One aspect of the usual depressive episode that is of importance in treatment is the fact that the episode tends to follow a curve, that is, tends to progressively worsen, then bottom out, and then progressively improve until the patient returns to his premorbid state. By determining the time of onset of the depression, the physician can make a rough estimate as to when an upward turn in the cycle may be expected. It is particularly important when assessing the efficacy of specific forms of treatment to take into account the spontaneous start of the upward swing.

There is some variation in the findings of the numerous studies relevant to duration. Undoubtedly, these variations may be attributed to different methods of observation and to different criteria for making diagnoses and judging improvement. In general, the relatively unrefined clinical studies (which will be discussed presently) indicate a longer duration than do the systematic studies.

Lundquist⁶ found that the median duration of the attack of depression in patients younger than 30 was 6.3 months, and for those older than 30, 8.7 months. This difference was statistically significant. There was no significant difference between men and women in regard to duration. (As noted previously, he also found acute onset associated with shorter duration.) Paskind⁴ also found in his outpatient group a shorter duration of attacks occurring before age 30 than after age 30. Rennie’s study yielded similar results, the first episode lasting on the average 6.5 months. He found, incidentally, that the average duration of hospitalization was 2.5 months. In Paskind’s series of non-hospitalized depressives, the median duration was 3 months. He found that 14 percent of the episodes lasted one month or less, and that almost 80 percent were completed in six months or less.

The earlier, less refined studies predominantly reported a period of 6–18 months as the average duration of the first attack: Kraepelin,¹ 6–8 months; Pollack,¹⁷ 1.1 years; Strecker et al.,¹⁰ 1.5 years. The clinical impression of writers of monographs on depression published in the 1950s and 1960s shows similar variation. Kraines¹⁸ stated that the average depressive episode lasts about 18 months. Ayd¹⁴ reported that prior to age 30, the attacks average 6–12 months; between ages of 30 and 50, they average 9–18 months; and after 50, they tend to persist longer, with many patients remaining ill from three to five years.

In regard to the duration of multiple episodes of depression, there was a prevalent opinion among the earliest clinicians of a trend toward prolongation of the episodes with each recurrence.¹ Lundquist, however, performed a statistical analysis of the duration of multiple episodes and found no significant increase in duration with successive attacks. Paskind’s⁴ study of outpatient cases similarly showed that the attacks do not become longer as the disease recurs. The median duration for first attacks was four months, and for second, third, or subsequent attacks three months.

The differences in the findings between the rough clinical studies and the statistical studies may reflect a difference in samples and/or different criteria for recovery from the depression. It is probable that certain biases influenced the selection of cases in the less refined studies and, therefore, the samples cannot be considered representative.

Lundquist found a significant association between prolonged duration and the presence of delusions in younger but not older patients. The presence of confusion, however, favored a shorter duration.

Brief Attacks of Manic-Depressive Psychosis (Bipolar Disorder)

In 1929, Paskind² described 88 cases of depression of very brief duration, from a few hours to a few days. These patients had essentially the same symptoms as those in his other extramural cases of longer duration and constituted 13.9 percent of his large series of cases diagnosed as manic-depressive disorder. The case histories he presented leave little doubt that they would later be diagnosed as neurotic-depressive (dysthymia) reaction.

TABLE 3-2. Frequency of Single and Multiple Attacks of Depression

Most of these patients with brief attacks also experienced longer episodes of depression. In 51, the brief attacks came first and were followed from months to decades later by longer attacks lasting from several weeks to several years. In 18, longer attacks occurred first, and were followed by the transient episodes. In nine, there were brief episodes only.

Recurrence

There is considerable variation in the older literature relevant to the frequency of relapses among depressed patients. Except as indicated, the statistics for manic-depressive psychosis include some manic patients in addition to the depressed patients. In the earlier studies, German authors reported a substantially higher incidence of recurrence than American investigators.⁶ These differences may be attributed to more stringent diagnostic criteria and to longer periods of observation by the German authors.

Of the more refined studies, Rennie’s reported relapse rate was closer to that of the German writers than to those of the other American investigators. He found that 97 of 123 patients (79 percent) initially admitted to the hospital in a depressed state subsequently had a recurrence of depression. (These figures do not include 14 patients who committed suicide after the first admission or who remained chronically ill.) When the cyclothymic cases (i.e., patients who had at least one manic attack in addition to the depression) are added to this group, the proportion of relapse is 142 patients of 170 (84 percent).

The Scandinavian investigators Lundquist⁶ and Stenstedt¹² reported, respectively, a 49 percent and a 47 percent incidence of relapse. In comparing their studies with Rennie’s, one can reasonably conclude that the more stringent diagnostic criteria employed by Rennie and the longer period of observation of his sample may account for the higher percentage of relapses in his report.

The differences in relapse rate are reflected in a striking difference in the rate of multiple recurrences. In Rennie’s series more than half of the depressed patients had three or more recurrences (see Table 3-2). The frequency of multiple recurrences in the cyclothymic cases was particularly high in Rennie’s series. Thirty-seven of the 47 patients in the group had four or more episodes. In Kraepelin’s series, 204 out of 310 cases of this type (67 percent) had one or more recurrences, with more than half having three or more attacks.

Another important aspect of the recurrent attacks is their duration. The opinion was frequently expressed that the episodes become progressively longer with each recurrence. Rennie, however, in analyzing his data, found that the second episode had the same duration as the initial episode in 20 percent, was longer in 35 percent, and was shorter in 45 percent. Paskind found that the median duration decreased with successive attacks.

Belsher and Costello¹⁹ reviewed 12 published studies of relapse in unipolar as opposed to bipolar depression. They selected studies that included correlates of relapse, rates of relapse, and a naturalistic follow-up period with no controlled maintenance therapy. They found a number of methodological inadequacies, such as unclear and variable definitions of recovery and relapse, nebulous patient characteristics, and vague inclusion and exclusion criteria. Despite these uncertainties, they were able to conclude that the risk of relapse in unipolar depression goes down the longer a person stays well. Several factors did predict relapse: (1) a history of depressive episodes, (2) recent stress, (3) poor social support, and (4) neuroendocrine dysfunction. Other variables did not predict relapse, including marital status, gender, and socioeconomic status.

Intervals Between Attacks

In examining the older literature on the intervals between episodes of depression, one is struck by the fact that recurrences may occur after years, or even decades, of apparent good health. The systematic studies offer little encouragement for the notion of a permanent cure analogous to the 5-year cures reported for cancer treatment. Recurrences have been reported as long as 40 years after remission from an initial depression.¹

The findings presented by Rennie, in particular, are noteworthy in that the highest proportion of relapses occurred 10–20 years after the initial episode of depression. His follow-up showed the following relapse rate for his 97 cases of recurrent depressions: less than 10 years after the first attack of depression, 35 percent; 10–20 years, 52 percent; more than 20 years, 13 percent. It should be emphasized that 65 percent had recurrences after remissions of 10–30 years.

In an earlier study, Kraepelin had tabulated the symptom-free intervals between 703 episodes of depression. Unlike Rennie’s study, Kraepelin’s included intervals after the second and later attacks (as well as intervals between the first and second episodes). He found that with each successive attack the intervals tended to become shorter. Since his series consisted of hospitalized patients, it is interesting to note the same trend among the extramural patients in Paskind’s study. A comparison of the distribution of intervals in ten-year categories is shown in Table 3-3. For the purposes of comparison, Rennie’s results are also included. It should be emphasized that his findings applied only to the first interval. The tendency for his intervals to be longer than Kraepelin’s and Paskind’s may be explained by the fact that the later intervals included in their study were shorter than the first intervals. Kraepelin and Paskind showed a somewhat similar distribution of the intervals, with Paskind’s outpatient cases having longer periods of remission than Kraepelin’s hospitalized cases.

TABLE 3-3. Distribution of Time Intervals Between Manic-Depressive Episodes in Inpatients and Outpatients

*Includes only first interval (between first and second episode).

TABLE 3-4. Median Intervals for Inpatients and Outpatients (years)

Another way of expressing the duration of the intervals is in terms of the median duration of the specific intervals. Table 3-4 shows that the median interval is longer in Paskin’s outpatient cases, and also that in both outpatient and hospitalized cases the median intervals tended to be shorter with successive attacks. In Kraepelin’s study, the biphasic cases showed consistently shorter symptom-free intervals than the simple depressions.

Further support for the observation that after the first recurrence the interval tends to become shorter is found in Lundquist’s study. In the age group older than 30, the mean duration of the first interval was about seven years, and the second interval three years. This difference was statistically significant.

Lundquist’s data, classified according to three-year intervals, showed that the overwhelming preponderance of relapses occurred in the first nine years. It should be pointed out that his follow-up period was as short as 10 years in some cases, as compared to 25–30 years in Rennie’s series. Hence, it is probable that many of the cases in Lundquist’s series would have shown a relapse if they had been followed for a longer period than 10 years. Lundquist computed the probability of a relapse after a patient has recovered from an initial episode of depression (Table 3-5). These findings were tabulated separately for the young depressives and older depressives, but no significant difference was found between the two groups. It may be noted that the highest probability of recurrence was in the 3–6-year interval.

TABLE 3-5. Probability of Recurrence After Remission from First Attack (%)

Adapted from Lundquist 1945.

TABLE 3-6. Outcome According to Clinical Criteria (%)

Adapted from Kiloh et al. 1988.

Outcome for “Endogenous” Versus “Neurotic” Depression

Kiloh et al.²⁰ studied the long-term outcome of 145 patients with primary depressive illness who were admitted to a university hospital between 1966 and 1970. Patients were categorized into endogenous and neurotic subtypes. The follow-up period was an average of 15 years later, and data were obtained on 92 percent of the patients. Table 3-6 shows the percentages of those who (1) recovered and remained well, (2) recovered but experienced subsequent depression, or (3) remained incapacitated or committed suicide.

Schizophrenic Outcome

In Rennie’s 1942 sample of 208 cases of manic-depressive psychosis, four cases changed their character sufficiently to justify the conclusion of an ultimate schizophrenic development. A review of these cases suggested that there was a strong component of schizophrenic symptomatology at the time of the diagnosis of manic-depressive psychosis.

At about the same time, Hoch and Rachlin²¹ reviewed the records of 5,799 cases of schizophrenia admitted to Manhattan State Hospital, New York City. They found that 7.1 percent of these patients had been diagnosed as manic depressive during previous admissions. Whether there was an alteration in the nature of the disorder, an initial misclassification, or a change in diagnostic criteria was not established by these writers.

Lewis and Piotrowski²² found that 38 (54 percent) of 70 patients, originally diagnosed as manic depressives, had their diagnoses changed to schizophrenia in a 3–20-year follow-up. In reviewing the original records, the authors demonstrated that the patients whose diagnoses were changed were misclassified initially, that is, they showed clear-cut schizophrenic signs at the time of their first admission. Because of the very loose criteria used in diagnosing manic-depressive disorder in the early decades of the twentieth century, it is difficult to determine what proportion, if any, of the clear-cut manic depressives had a schizophrenic outcome.

Lundquist reported that about 7 percent of his manic-depressive cases eventually developed a schizophrenic picture.

Astrup et al.¹¹ isolated 70 cases of “pure” manic-depressive disorder and followed these 7–19 years after the onset of the disorder. They found that none had a schizophrenic outcome. In contrast, 13 (50 percent) of a group of 26 cases diagnosed as schizoaffective psychosis showed schizophrenic symptomatology on follow-up.

Suicide

At the present time, the only important cause of death in depression is suicide. (The general topic of suicide is broad, and many excellent monographs are available, e.g., Farberow and Schneidman,²³ Meerloo.²⁴) Previously, inanition due to lack of food and secondary infection were occasional causes of death, but with modern hospital treatment such complications are less usual.

The actual suicide risk among depressed patients is difficult to assess because of the incomplete follow-ups and difficulties in establishing the cause of death. Long term follow-ups by Rennie⁵ and by Lundquist⁶ indicated that approximately 5 percent of the patients initially diagnosed in a hospital as manic depressive (or as having one of the other depressive disorders) subsequently committed suicide.

In the mid-twentieth century, several studies demonstrated comparatively higher suicide rates among depressed patients. Pokorny²⁶ investigated the suicide rate among former patients in a psychiatric service of a Texas veterans’ hospital over a 15-year period. Using a complex actuarial system, he calculated the suicide rates per 100,000 per year as follows: depression, 566; schizophrenia, 167; neurosis, 119; personality disorder, 130; alcoholism, 133; and organic, 78. He then calculated the age-adjusted suicide rate for male Texas veterans as 22.7 per 100,000. The suicide rate for depressed patients, therefore, was 25 times the expected rate and substantially higher than that of other psychiatric patients.

Temoche et al.,²⁷ studying the suicide rates among current and former mental institution patients in Massachusetts, found a substantially higher rate of suicide among depressed patients than nondepressed patients. The computed ratio for depressives was 36 times as high as for the general population and about three times as high as for either schizophrenics or alcoholics.

The suicide rate among patients known to be suicidal risks is apparently high. Moss and Hamilton²⁸ conducted a follow-up study for periods of two months to 20 years of 50 patients who had been considered “seriously suicidal” during their previous hospitalization (average 4 years). Eleven (22 percent) of the 50 later committed suicide. In a retrospective study of 134 suicides, Robins et al.²⁹ found that 68 percent had previously communicated suicidal ideas and 41 percent had specifically stated they intended to commit suicide.

The figures available at that time clearly indicated that the suicidal risk was greatest during weekend leaves from the hospital and shortly after discharge. Wheat,³⁰ surveying suicides among psychiatric hospital patients, found that 30 percent committed suicide during the period of hospitalization, and 63 percent of the suicides among the discharged patients occurred within one month after discharge. Temoche et al.²⁷ calculated that the suicidal risk in the first six months after discharge is 34 times greater than in the general population and in the second six months about nine times greater. About half of the suicides occurred within 11 months of release.

Many earlier studies reported the observation that women depressives attempted suicide more frequently than men but that men were more often successful. Kraines¹⁸ reported that, in his series of manic-depressive patients, twice as many women as men attempted suicide and three times as many men as women were successful suicides.

Although no data are available regarding the suicidal methods employed by depressives, recent statistics for the general population may be relevant. In 2001 intentional self-harm (suicide) by discharge of firearms was 16,869. By other and unspecified means, the number was 13,753. The ratio of male to female was 4.6 to 1; Black to White .5; Hispanic to non-Hispanic .5.³¹

There is evidence that the number of suicides each year in the United States is greater than the official 2001 report of 30,622. Many accidental deaths actually represent concealed suicides. For instance, in 1962 MacDonald³² reported 37 cases of attempted suicide by automobile. Writers believed that the actual rate of suicide was three or four times as great as the official rate. The number of attempted suicides was believed to be seven or eight times the number of successful suicides.³³

Homicide may occur in association with suicide among depressed patients.³⁴ Reports, for example, of parents killing their children and then themselves are not rare. One woman, convinced by her psychotherapist that her children needed her even though she believed herself worthless, decided to kill them as well as herself to “spare them the agony of growing up without a mother.” She subsequently followed through with her plan.

Several factors contribute to the risk of attempted or completed suicide. Risk is especially high during a major depressive episode in those with psychotic symptoms, previous suicide attempts, a family history of completed suicides, and concurrent substance use.^35,36 The best indication of a suicidal risk is the communication of suicidal intent.²⁹ Stengel³³ pointed out that the notion that the person who talks about suicide will never carry it out is fallacious. Also, a previous unsuccessful suicidal attempt greatly increases the probability of a subsequent successful suicidal attempt.^36,37 Brown et al.³⁸ were able to reduce repeat suicide attempts by 50 percent through the application of cognitive therapy, compared to usual care of tracking and referral services. They also were able to reduce depression severity and hopelessness (see Chapter 15).

Over a 5-year follow-up period, Klein et al.¹⁵ found that suicide attempts were made by 19 percent (16 of 84) of patients with chronic depression, and one of these resulted in actual suicide. In this study, there were no attempts among 37 patients with episodic disorder only. This suggests that the rate of suicide attempts increases in cases of chronic depressive illness (dysthymic disorder) compared to episodic major depression.

In addition to trying to elicit suicidal wishes from the depressed patient, the clinician should look for signs of hopelessness. In our studies we found that suicidal wishes had a higher correlation with hopelessness than with any other symptom of depression. Furthermore, Pichot and Lempérière,³⁹ in a factor analysis of the Depression Inventory, extracted a factor containing only two variables, pessimism (hopelessness) and suicidal wishes.

Suicide Risk in Bipolar Disorder

Fagiolini et al.⁴⁰ found suicidal thinking and behavior to be common in individuals with bipolar disorder. The people in the study were 175 patients with bipolar I disorder who were participating in a randomized controlled trial, the Pittsburgh Study of Maintenance Therapies in Bipolar Disorder. Suicide had been attempted by 29 percent of the patients prior to entering the study.

The method used in this study was to compare clinical and demographic characteristics of those who had attempted suicide before entering the study to those who had not attempted suicide. Among the conclusions was that greater severity of bipolar disorder and higher body mass predicted a history of suicide attempts. Severity was defined as a greater number of previous depressive episodes, as well as higher scores on an evaluator-rated measure of depression (Hamilton Rating Scale—25 items).⁴⁰

Predictors of Chronic Depression

Riso et al.⁴¹ reviewed the studies of determinants of chronic depression. They reported that such determinants have not been adequately elucidated, but that studies have considered six possible factors: (1) developmental factors such as childhood adversity (early trauma or maltreatment), (2) personality and personality disorders like neuroticism (emotional instability or vulnerability to stress) and stress reactivity, (3) psychological stressors, (4) comorbid disorders, (5) biological factors, and (6) cognitive factors. In what follows, we summarize their findings.

Developmental Factors

Among the developmental factors, there is some evidence for the importance of early trauma or maltreatment but not for early separation and loss.

Personality Disorders

In 11 studies comparing personality rates in dysthymia to major depression, patients with dysthymia were found to have higher rates of personality disorders. However, as of 2002 only one prospective study had been carried out. The two conditions may share causal factors, rather than dysthymia developing as a consequence of personality disorder.

Psychological Stressors

Concerning psychological stressors, the duration of chronic depression makes it more difficult to disentangle stressors that may lead to prolongation of depression from the effects of depression itself in generating stressors. Riso et al.⁴¹ noted that the APA diagnostic manuals assert that dysthymic disorder is associated with chronic stress, but that it is possible that the two studies supportive of this may be confounded by patient perceptions of stressors rather than actual events. Supportive of this is that treatment with antidepressant medications modifies reports of daily hassles.

Comorbid Disorders

Findings on comorbid disorders include one study suggesting that chronic illness in a spouse can lead to dysthymia. Also, dysthymia has been found associated with several psychiatric conditions, including anxiety and substance abuse, with social phobia the most common.

TABLE 3-7. Cognitive Variables in Chronic Depression (CD), Nonchronic Major Depressive Disorder (NCMDD), and Never Psychiatrically Ill Controls (NPI)

Adapted from Riso et al. 2003.

Biological Factors

Biological factors are considered more fully in Chapter 9. With respect to predicting a chronic course of depression, neuroendocrinology studies have found that the disturbances in the hypothalamic-pituitary-adrenocortical axis in chronic depression are similar to those in nonchronic types. Also, no consistent differences in sleep physiology have been found to be related to course. Immunology studies suggest increased natural killer cell activation in both dysthymia and major depression, but the overactive immune response in dysthymia may be more trait-like compared to nonchronic depression.

Cognitive Factors

The role of cognitive factors in chronic depression is “perhaps the most understudied area.”⁴¹ However, one study found that several cognitive variables differentiated chronically depressed individuals from those with major depression.⁴² The study included 42 outpatients with chronic depression (CD), 27 outpatients with nonchronic major depressive disorder (NCMDD), and 24 never psychiatrically ill controls (NPI). The cognitive variables included a Schema Questionnaire, the Dysfunctional Attitudes Scale, the Attributional Style Questionnaire, and a ruminative response style questionnaire (see Table 3-7).

Results showed that the two depressed groups were elevated on every cognitive measure compared to the control group. The depressed groups were higher on the schema clusters, dysfunctional attitudes, stable and global attributional style, and rumination. Moreover, the chronic depression group compared to the nonchronic group was significantly elevated on all cognitive measures except for ruminative response and attributional style. In general, the chronic group of patients were more elevated on measures of cognitive variables even after taking into account (statistically controlling for) mood state and personality disorder symptoms. Thus, this preliminary study suggests that the cognitive perspective may be of some utility in distinguishing between those with chronic depression compared to nonchronic major depressive disorder.

Overall, Riso et al.⁴¹ concluded by suggesting that continued research is needed with (1) better definitions of chronicity, (2) utilization of more appropriate comparison groups, and (3) prospective follow-up studies across longer time periods. To more completely ascertain the causes of chronic depression is one of the most important areas for researchers in the field of experimental psychopathology.

Conclusions

1. In naturalistic studies, complete remission from an episode of depression occurs in 70–95 percent of the cases. About 95 percent of the younger patients remit completely.

2. When the initial attack occurs before age 30, it tends to be shorter than when it occurs after 30. Acute onset also favors shorter duration.

3. After an initial attack of depression, 47–79 percent of the patients will have a recurrence at some time in their lives. The correct figure is probably closer to 79 percent, because this is based on a longer follow-up period.

4. Individuals who have experienced a major depressive disorder, single episode, have at least a 60 percent chance of having a second episode; those who have had two episodes have a 70 percent chance of a third; and those with three prior episodes have a 90 percent chance of having a fourth.³⁵

5. The likelihood of frequent recurrences is greater in the biphasic cases than in cases of depression without a manic phase. Between 5 and 10 percent of individuals with major depressive disorder, single episode, later develop a manic episode.³⁵

6. Although the duration of multiple episodes remains about the same, the symptom-free interval tends to decrease with each successive attack. In the biphasic cases the intervals are consistently shorter than in the simple depressions.

7. Approximately 5 percent of hospitalized bipolar patients subsequently commit suicide. The suicidal risk is especially high on weekend leaves from the hospital and during the month following hospitalization and remains high for six months after discharge.

8. The rate of suicide attempts appears to be higher among those with chronic depressive illness (dysthymic disorder) compared to episodic major depression.

9. The notion that a person who threatens suicide will not carry out the threat is fallacious. The communication of suicidal intent is the best single predictor of a successful suicidal attempt. Previously unsuccessful suicidal attempts are followed by successful suicides in a substantial proportion of the cases.

10. Suicide risk in patients with bipolar disorder is increased in those with greater severity and higher body mass.

11. The search for determinants of chronic depression includes developmental factors like childhood adversity (early trauma or maltreatment); personality, psychological stressors, comorbid disorders, biological factors, and cognitive factors. In studies of chronic depression, the strongest evidence of etiology is developmental factors, with some support for chronic stressors and stress reactivity.

12. The role of cognitive factors in chronic depression is “perhaps the most understudied area.”⁴¹ However, one study suggested the cognitive perspective may be of some utility in distinguishing between chronic and nonchronic forms of depressive disorder.