Full depressive syndrome and inner unrest are both essential elements of this
syndrome. The presence of motor agitation is sufficient to make the diagnosis,
as in the RDC criteria, because it also confirms the presence of psychic agitation.
The absence of motor agitation creates the diagnostic problem of distinguishing
anxiety from the particular inner unrest of agitated depression. In order to
clarify the differential diagnosis between anxiety and inner agitation, pending
more systematically validated criteria, we used a set of criteria different
from that proposed in our previous paper (Koukopoulos, 1999). Along with major
depression and inner agitation, at least three of the following symptoms must
be present: (1) Racing or crowded thoughts; (2) irritability
or unprovoked feelings of rage; (3) absence of signs of motor
retardation; (4) talkativeness; (5) dramatic
descriptions of suffering or frequent spells of weeping; (6) mood
lability and marked emotional reactivity; and (7) early insomnia.
Such symptoms are of excitatory, not depressive, nature and indicate the absence
of inhibition. Early insomnia is often sustained by racing or crowded thoughts.
These criteria were, however, validated by the external criterion of the effect
of antidepressant treatments. A total of 53% of cases in a previous study (Koukopoulos
et al., 2004) had simple depressions that became agitated (with at least three
of the above symptoms) when treated with antidepressants.
Spontaneous and induced agitated depression
We previously presented 212 (152 women; 72%) patients suffering from agitated
depression as defined above (Koukopoulos et al., 2004). All met DSMIII-R
criteria for major depression. Sixty-seven cases presented with agitated
depression (non-psychotic) with psychomotor agitation. The others suffered
from minor agitated depression (77 cases), as defined above, and psychotic
agitated depression (68 cases). According to their previous course, 56 (27%)
were BPI, 66 (31%) were BPII, 68 (32%) were unipolar (UP) and in 22 patients
(10%) their first affective episode was an agitated depression. The age at
index episode of agitated depression was 44.9 for women and 44.5 for men.
One hundred and eleven patients had had earlier episodes of agitated depression.
In these cases the episode started as an agitated depression in 99 (47%)
cases. In the other 113 (53%) cases the episode started as a simple depression
without symptoms of agitation, and later it turned into an agitated depression.
The mean duration of the simple depression was 4.7 months (1–36 months).
The shift from simple to agitated depression occurred in association with
various treatments, mainly antidepressants, but also other treatments with
stimulant effect. The onset of agitated depression took place either immediately
or within a few days to a few weeks. The great majority of agitated depressions
emerged during treatment with tricyclic antidepressants (TCA’s) (58
cases), SSRI’s (45 cases), other antidepressants (27 cases), and seven
cases during maintenance treatment with antidepressants. The small number
of cases (four) associated with monoamine oxidase inhibitors (MAOI’s)
is probably due to the limited use of these agents in Italy, but the possibility
that these agents may be less agitating cannot be ruled out. Six cases were
associated with steroids, four with levothyroxine, four with excessive caffeine
intake, four with lithium withdrawal, and two with neuroleptic withdrawal.
Eighty-three women (55% of all women) and 30 men (50% of all men) became
agitated in association with the above-mentioned treatments. The previous
course of these 113 patients was: BPI for 27 patients, BPII for 47 patients,
unipolar depression for 34 patients and five were first affective episodes.
If we compare them to the total numbers of the different groups we find that
48% of the BPI patients, 71% of the BPII, and
50% of the unipolar patients had induced agitated depressions. The preponderance
of BPII patients is to be noted. The age at onset of the mixed episode was
48.4 years for the induced group and 41.7 years for the spontaneous group.
The duration of the mixed episode was four months for the induced group and
5.4 months for the spontaneous group. There was no difference between the spontaneous
and induced groups with regard to severity or outcome.
Among our 212 agitated depressions, 68 (47 women and 21 men)
also had psychotic symptoms. As psychotic symptoms we considered hallucinations,
delusions, both congruent and non-congruent (true delusions and not mere fears
or doubts), and the presence of a state of mental confusion and grossly disturbed
behavior. Of these patients, 22 (32%) were spontaneous, that is, the psychotic
symptoms emerged spontaneously and not in association with pharmacological
treatment. In the other 46 patients, the psychotic symptoms emerged in association
with antidepressant treatment. Of these 46 patients, 30 patients had a BPI
course (54% of all BPI patients), 14 had a course of BPII (21% of all BPII
patients), 19 had a previous course of recurrent depression (28% of all unipolar
patients), and five were first affective episodes of psychotic depression.
It should be underlined that all the 14 BPII patients who had a psychotic agitated
depression were all induced by antidepressants.
Latent agitated depression and the issue of antidepressant-induced
As described above, there are many cases of depression that, though without
manifest psychic or motor agitation and without psychosis, rapidly become agitated
after the institution of antidepressant drug treatment. All antidepressants
can induce this effect in certain patients but in our clinical experience the
most rapid triggering is seen with SSRIs. Probably the cases of suicidal or
other violent acts attributed to SSRIs and other antidepressants in recent
years may be due to the agitation induced by the drugs in patients who were
already agitated or prone to agitation. Reading the clinical descriptions of
these cases, it is clear that the suicidal ideas have emerged from a state
of agitated depression (Healy, 1994; Teicher, Glod & Cole, 1990), the
psychomotor component of which is often seen as akathisia (Drake & Ehrlich,
1985; Rothschild & Locke,
1991). Clinicians often consider the emergence of agitation as an adverse reaction,
but it is clearly the emergence of a new syndrome, just as in the case of antidepressant-induced
mania. This modification of the depressive syndrome is of great concern not
only for its inherent risks, but also given the fact that it is iatrogenic.
We propose the term latent agitated depression for these depressions
prone to agitation. How can they be identified or at least suspected? According
to our observations, the most reliable signs are: 1. Total
lack of inhibition in speech and movement; 2. A certain mental
vivacity unusual to inhibited depression; 3. Rich description
of their depressive suffering; 4. Early or middle insomnia
rather than late insomnia. These signs are not of absolute value but may suffice
to suspect a latent agitated depression and make the clinician more cautious
with treatment. Treatment should commence with an anti-manic (small doses of
anti-psychotics, anti-epileptics or lithium) and/or anxiolytic. If antidepressants
are used from the beginning, one of the above-mentioned agents should be added.
Indeed, sedating treatments are the best protection against suicide (Fawcett,
Clark & Busch,
Psychic and motor agitation, racing or crowded thoughts, irritability or unprovoked
feelings of rage, talkativeness, mood lability and early insomnia are clearly
symptoms of nervous excitability and when they are mixed in the picture of
a major depressive episode, they constitute a mixed depressive episode. The
adverse response of these states to antidepressant drugs, above all the increase
of agitation and of suicidality, makes a clear distinction between simple
and mixed depression necessary and urgent. Treatment should initiate with
anti-psychotics, anti-epileptics, lithium and benzodiazepines and when agitation
has subsided, if simple depression persists, antidepressants could be used
- Koukopoulos, Athanasios et al; Mixed Depressive States: Nosologic and Therapeutic
Issues; International Review of Psychiatry; Feb 2005, Vol. 17 Issue 1, p 21
Diagnosis and Treatment of Bipolar Disorders in Adults:
A Review of the Evidence on Pharmacologic Treatments
- Jenn, M. W. (2014). Diagnosis and Treatment of Bipolar Disorders in Adults: A Review of the Evidence on Pharmacologic Treatments. American Health & Drug Benefits, 9(7). p. 489-499.
Reflection Exercise #6
The preceding section contained information
about diagnostic criteria for mixed depression in a bipolar client. Write
three case study examples regarding how you might use the content of this section
in your practice.
What are the most reliable signs of depression prone to agitation? To select and enter your answer go to Test.