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Treating the Highs & Lows of Bipolar Adults
Bipolar Adults continuing education psychology CEUs

Section 20
Diagnostic Criteria for Mixed Depression in a Bipolar Client

CEU Question 20 | CEU Answer Booklet | Table of Contents | Bipolar
Counselor CEUs, Social Worker CEUs, Psychologist CEs, MFT CEUs

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 suicidality
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, 1993).

Conclusions
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 cautiously.
- Koukopoulos, Athanasios et al; Mixed Depressive States: Nosologic and Therapeutic Issues; International Review of Psychiatry; Feb 2005, Vol. 17 Issue 1, p 21
The article above contains foundational information. Articles below contain optional updates.

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Personal 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.

Online Continuing Education QUESTION 20
What are the most reliable signs of depression prone to agitation? Record the letter of the correct answer the CEU Answer Booklet.

 
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