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ironic that today agitated depression has lost its status as a mixed state, whereas
manic stupor and dysphoric mania are still considered as such.

Clinical picture of agitated depression
Depressed anxious mood and inner, psychic agitation dominate the clinical
picture. Psychomotor agitation is present in many cases, but not in all. In the
167 Agitated depression: spontaneous and induced

cases without psychomotor agitation, the inner unrest is the main symptom. This
inner agitation makes the patient very anxious and fearful, hence the condition is
very difficult to distinguish from anxiety, as will be discussed later. The inner
unrest manifests itself with irritability or feelings of unprovoked rage, racing or
crowded thoughts, talkativeness, and dramatic descriptions of psychic pain. A
typical feature of agitated depression is the absence of retardation in speech and
movement; yet, there is an inhibition of purposeful activity, which in more severe
cases is nearly complete. In mild forms, the patient is quite active and sometimes
anxiously hyperactive. Complete anhedonia and lack of interest are marked in all
cases. Psychic pain is particularly severe and is often accompanied by suicidal
thoughts and impulses. In more severe forms, the psychic pain is constant while in
milder cases there is lability of mood and emotional reactivity. Early insomnia,
often sustained by racing thoughts, is common.

Clinical forms of agitated depression
The following clinical forms can be distinguished.

Psychotic agitated depression
These patients present with depressed mood, restlessness, anxiety, delusions of
guilt and persecution, hypochondriacal ideas and, often, strong suicidal impulses.
The similarity of this syndrome with that of other psychotic depressions that
do not present with motor agitation is notable (Nelson and Bowers, 1978;
Frances et al., 1981). In the latter, the patient lies silently in bed. On questioning,
the patient describes an intense inner agitation, often located in the chest, abdomen,
or head. A young patient said he felt ˜˜blades ripping through his guts™™ “ a similar
image to that employed by Hippocrates. Some patients describe racing or crowded

Agitated depression (non-psychotic) with psychomotor agitation
Patients do not present with delusions or hallucinations. The picture is dominated
by depression, anxiety, and motor agitation similar to that described in the RDC
criteria (Spitzer et al., 1978). The patient may complain of crowded thoughts.

Minor agitated depression
The patient does not appear outwardly agitated, or the motor agitation is limited,
but there is total lack of retardation. The patient speaks fluently and moves normally.
The patient complains of intense inner agitation. The psychic pain of the patient
is relentless, and the patient feels unable to perform normal tasks or enjoy
anything. Frequently the patient complains of racing or crowded thoughts
168 A. Koukopoulos et al.

Table 7.1 Minor agitated depression

Patient displays: Patient complains of: Partner reports:
Depressed mood Anxiety Continuous complaining
Psychic agitation Inner tension Occasional overt expression of
Vivacious facial expression Muscular tension, subjective
feelings of irritability and
unprovoked feelings of rage
Dramatic descriptions of Crowded or racing thoughts Occasional sexual hyperactivity
Lack of retardation Early or middle insomnia
Spells of weeping Suicidal ideas and impulses
High diastolic blood pressure
Emotional lability
Impulsive suicidal attempts

(Table 7.1). We propose the term minor agitated depression or minor mixed depres-
sion because the syndrome is less severe and requires lower doses of medication.
The term minor agitated depression is replacing the term excited anxious depres-
sion proposed by us in the past (Koukopoulos, 1999). We are now proposing the
term minor to indicate the lesser severity in comparison with the other two forms
and because it is simpler. This syndrome is similar to Kraepelin™s (1913) depression
with flight of ideas and Lange™s excitable depression (Lange, 1928), as described
These patients fully meet the DSM-III criteria for major depression. Because of
the absence of psychomotor agitation, they do not meet the RDC criteria for
agitated depression and do not meet the criteria for a DSM-IV mixed affective
episode because of the absence of a clear manic syndrome. Yet this form should be
considered as a mixed state not only for the racing thoughts that are undoubtedly a
sign of excitation, for the irritability, and for the emotional lability, but also for the
course of this disorder and the reaction to antidepressant treatment. Because of the
lack of inhibition and because of the intense expression of their suffering, these
patients are often diagnosed as presenting with reactive or personality disorders.
The syndrome may resemble hysteroid dysphoria (Liebowitz and Klein, 1981; Klein
and Liebowitz, 1982) because of the vivacious expression of their suffering. These
syndromes may occur spontaneously or appear during antidepressant treatment.
169 Agitated depression: spontaneous and induced

An interesting split is often observed between motor agitation and racing or
crowded thoughts. Their relationship appears to be inversely proportional. Mental
excitement is more frequent and more intense in patients who do not show
marked motor agitation. There is a striking analogy with manic states, in which
the presence of delusional ideas is inversely proportional to psychomotor excite-
ment. This phenomenon may have played a decisive role in the success of political
and religious fanatics who created a vast popular following. It can be assumed that,
if their delusional or semidelusional ideas had been accompanied by patent motor
excitement, they would not have had the same charismatic influence on their
Because the term agitation usually means motor agitation, as in the RDC, and
neglects the cases of mental and psychic agitation, the term mixed depression
(MxD) is suggested for all the clinical forms of agitated depression.
It is also suggested that the old term melancholia be reused for the psychotic
form of agitated depression. This name not only represents a great psychiatric
tradition, but also fully conveys the tragic human experience of these patients and
bears out a deeply significant fact “ that the major psychiatric syndromes have
remained unchanged over the course of thousands of years. If they are not disease
entities, they surely are what Kraepelin would have called natural realities.

Flight of ideas, racing and crowded thoughts
In all three forms of agitated depression delineated here, many patients complain
of a disturbance of the train of thought that they call crowded or racing thoughts
or other similar names. In the literature, this is often called depression with flight of
ideas. This disturbance is, in many respects, different from the flight of ideas
observed in manic state.
Flight of ideas in manic patients is expressed verbally in an abundance of words
or pressured or clearly logorrheic speech. When racing thoughts are present in
depressed patients, speech is limited or at normal tempo.
In flight of ideas, the content of these ideas and somehow the pattern of
thoughts are reflected in the content and pattern of the speech itself. In racing
thoughts, there is not such a close relationship. On the contrary, the patient talks
about the thoughts and reports on their course and their content and his or her own
sensations. Racing thoughts are not expressed directly in the speech. The patient
repeats monotonous laments, but the great energy involved in these depressive
lamentations and in this speech denote the mixed depressive“manic nature of this
symptom. In some cases, there is a certain degree of pressured speech.
The agitated melancholic patient complains of this course of thought as a
torment, but the exalted (manic) patient never complains about his or her flight
170 A. Koukopoulos et al.

of ideas. This observation by Richarz, in 1858 in his paper on melancholia agitans,
is fully confirmed by the patients seen today.
Richarz (1858) also observed that in mania thoughts tend to form strings of
ideas (Reihenbildung von Vorstellungen) that link together by their content,
alliteration, or assonance. In racing thoughts, the ideas come and go rapidly as if
they were hunting each other or continuously overlapping without any link
between them.
In Braden and Qualls™ (1979) work, the phenomenon is described by their
patients with metaphors implying rotation: like a whirlpool, a hurricane, a cen-
trifuge. A patient of the authors said, ˜˜I felt like the thoughts were circling around
in my head and somehow I felt trapped by them.™™ Another young woman said her
thoughts were ˜˜like a raging river breaking through a dam and flooding my mind.™™
In other cases, the phenomenon could be called crowded thoughts; the patient
complains that his or her head is full of thoughts of all kinds, not merely depressive
ones and sad memories, but prevalently trivial thoughts of little significance for the
patient. Not infrequently, patients report the presence of musical tunes that they
keep hearing in their heads. The most important feature of these crowded or racing
thoughts is that they afflict the patient not only through their meaning but also by
the way they manifest themselves; there must be something unrelentingly painful
and oppressive in their impact on the patient™s mind.
A male patient said, ˜˜I felt attacked by them.™™ Another male patient who tried
unsuccessfully to shoot himself in the head said afterwards that he did it to stop his
thoughts. This patient was of depressed mood and kept quiet. These kinds of
thoughts are typically intense at night and often prevent the patient from falling
Depressive ruminations are different. They consist of only a few thoughts that
carry the anxieties and fears of the patient, and they are constantly present or recur
frequently. The patient complains of their content but not of their course. There
are naturally cases of transition between crowded thoughts and ruminations, and
making the distinction may be difficult.
Flight of ideas, racing thoughts, and crowded thoughts are clearly excitatory
phenomena. Neuronal hyperactivity must underlie them. This hyperactivity is
dramatically confirmed by the effect of antidepressant medication, especially given
without typical and atypical neuroleptics. The thoughts are further accelerated and
intensified; the patient becomes exasperated to such a point that sometimes he or
she wants to commit suicide. This worsening may be induced within the space of a
few days or even hours. In many cases, the suicidal impulses induced by anti-
depressants seem to be linked to the acceleration of the thoughts and to the
worsening of the agitation. Typical and atypical neuroleptics, on the contrary,
are of great benefit.
171 Agitated depression: spontaneous and induced

Restlessness, inner agitation, and anxiety

I was awfully restless, I kept wringing my hands and pulling my hair. I couldn™t sit still but had to
keep pacing around all the time. I was not able to read or listen to music, I couldn™t play the
piano, I couldn™t concentrate at all, I was unable to eat or sleep. I was irritable and constantly
tired, I suffered from fears of going insane, of having contracted AIDS or syphilis and these
thoughts would not leave me alone. I started thinking of oblivion, about suicide. I was so restless
that I began to think of ending my life just to get some peace of mind.

This young woman called her agitated depression a horror.
Other patients exhibit much less psychomotor agitation, but they clearly suffer
from inner agitation. They describe it as intense inner tension and use metaphors
such as ˜˜I feel like I™m bursting inside,™™ or ˜˜I feel a violent force inside me as if I
wanted to smash everything,™™ or ˜˜I feel there are blades tearing through my guts.™™
They describe an internal shaking or an electrical current passing through the
body. This tension is also manifested as muscular tension or pains. Diastolic blood
pressure is found typically increased to 90 or 100 mmHg. Psychomotor agitation
and inner agitation are equally significant. Both are worsened by antidepressants
and improved by neuroleptics. Psychic agitation is a subjective symptom, but it
has objective manifestations observable by others, and the descriptions given by
the patients are so characteristic as to make this symptom as reliable as any other
aspect of affect and mood.
Closely related to this inner tension and agitation is a feeling of rage arising
without external provocation and in most cases not directed against anything. The
patient just complains about it. In other cases, there is irritability and, at times,
verbal and rarely physical violence, usually within the family environment, as
noted by Lange (1928). In extreme cases, this rage, combined with hopelessness,
is the cause of the violent character of suicide attempts, of which raptus melancho-
licus is the utmost example. At least some suicide“homicide cases are due to
agitated depression. The difference from manic aggressiveness is that in manic
patients anger is provoked by some external cause and is directed outward.
The clinical picture comprises depressed mood, total anhedonia, exhaustion,
and inability to perform simple tasks or take part in usual activities, and it is
marked by intense anxiety and fears “ fear of everything or psychotic fears, often
hypochondriacal, especially the fear of losing one™s mind. The devil figures fre-
quently in these fears. One of the most common colloquial expressions for feeling
low and fearful is ˜˜the blues,™™ which originates from an old English expression
alluding to an attack by ˜˜the blue devils.™™
Anxiety seems highly related not only to psychomotor agitation, but also to
inner, psychic agitation. An interesting debate on anxiety in manic-depressive
172 A. Koukopoulos et al.

insanity, and particularly on melancholia agitata, took place at the beginning of the
twentieth century, between Westphal and Koeplin (1907) on one side and Specht
(1908) on the other. The former authors, following Wernicke (1906), who con-
sidered anxiety the basis of Angstpsychosen, maintained that anxiety overwhelms
depressive inhibition and dominates the clinical picture, producing restlessness,
agitation, and flight of ideas. Wernicke believed that the increased production of
anxious thoughts could lead to flight of ideas, pressured speech, and agitation. A
similar idea was advanced by Weitbrecht in 1963. Mentzos (1967), in his mono-
graph on mixed states in 1967, proposed a distinction between anxious agitated
depression and excited depression with flight of ideas.
Specht (1908) saw agitation and flight of ideas as manic elements and consid-
ered melancholia agitata and agitated depression as mixed manic-depressive states.
He made the same assessment of melancholic delusions and proposed classifying
every mixed state with depressive mood as melancholia. As far as anxiety is
concerned, he thought that the inhibition present in depressions of circular
insanity dampens the anxiety, which is, on the contrary, freely manifested in
cases without inhibition. Inhibition depresses all emotions and reactions, but
anxiety is often completely absent in retarded depression. The anxiety found in
typical depression (major depressive episode) is an emotional reaction to the
painful experience of the depression itself. Human beings react with anxiety to
stress factors of much lesser entity. This anxiety improves with antidepressant
medication. Often, it is the first symptom to disappear.
The anxiety observed in agitated depression seems to be of a different kind,
inherent in the agitation itself. These two types of anxiety, assessed with limited
semiologic tools, seem almost identical. The subjective suffering is similar, and
they produce the same fears. Yet the anxiety present in agitated depression appears
to be a form of excitation or arousal. By more careful examination of the patients,
a substantial difference emerges between on the one hand the anxiety of anxiety
disorders, which consists of a feeling of apprehension, fearfulness, or impending
doom, and the anxiety that often accompanies depressive episodes, which consists
of fear of being worthless, fear of facing others, and fear of not getting better, in
short, fear of something, and on the other hand, the inner tension of agitated
depression. This latter anxiety seems similar to the two former types of anxiety but
is substantially different. Patients of considerable introspective capacity describe
this inner agitation as a great energy that strikes and possesses their minds and
sometimes their bodies too, in a way that annihilates their capacity to think, feel,
concentrate, or do anything.
Racing thoughts have the same annihilating effect, probably because they are
conveyed by this abnormal energy. It becomes impossible for the patient to cope
with all of this because of the overwhelming sensation of total impotence. The total
173 Agitated depression: spontaneous and induced


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