Neuroleptic-Induced Akinesia
The extrapyramidal side effect of neuroleptic-induced akinesia has had more than one definition in the literature, and this can be a confusing point. The original definition, and the one that is easiest to recognize, involves stiffness with cogwheel rigidity of large muscle groups, leading to typical parkinsonian posture, shuffling gait, and reduction of accessory motor movements (Chien et al. 1984).

These symptoms are gross, and the diagnosis of this type of akinesia is relatively easy. A later definition, originally formulated by Rifkin et al. (1975, 1978) and elaborated by Van Putten and May (1978), is more subtle but describes an equally debilitating condition (Bermanzohn and Siris 1992; Martin et al. 1985). This form of akinesia, also extrapyramidal in origin, involves a reduction in the basal ganglia’s ability to initiate and sustain behavior. Patients with this form of akinesia may or may not have decreased accessory motor movements, but behaviorally they are “like bumps on a log” and act as if “their starter motor is broken.” If they are watching television, for example, they are likely not to get up spontaneously and do something else at the end of the show they are watching. Rather, they are likely to “just sit.”

In fact, if the condition is severe, they are likely not to even have the spontaneity to change the channel to find a show they like. They also appear to lack initiative socially-a problem that may be manifested by a lack of ordinary interpersonal behaviors such as starting conversations in appropriate situations. Blue mood has also been noted to accompany this state. Obviously, when asked about their condition, patients with this form of akinesia are likely to report anhedonia, self-blame, and the subjective state of lack of energy (a state easily confused with depression).

Indeed, it is unfortunate that a large proportion of the studies that have examined the incidence or treatment of depression in patients with schizophrenia have not appropriately considered the possibility of this form of akinesia as a confounding factor and controlled for it either by a reduction in neuroleptic dose or by concomitant administration of full doses of antiparkinsonian medications.

Neuroleptic-Induced Akathisia
A second extrapyramidal neuroleptic side effect that is easy to diagnose in its blatant form but that in its more subtle form can easily be confused with depression is akathisia (Siris 1985; Van Putten 1975). In akathisia, it is “as if the patient’s starter motor won’t shut off.” Prominent motor restlessness makes the blatant form of this side effect obvious. Subtle forms can be more difficult to recognize, manifesting as a more modest propensity for increased motor behavior, perhaps some degree of wandering or overtalkativeness, or more excessive behavioral responses in situations than otherwise would occur.

In some patients, this can appear to be agitation. Importantly, akathisia is often experienced by patients as substantially dysphoric (Halstead et al. 1994; Van Putten 1975), and, indeed, akathisia has been associated with both suicidal ideation and suicidal behavior (Drake and Ehrlich 1985; Shear et al. 1983). Like akinesia, akathisia is likely to respond to a lowering of the neuroleptic dosage, if that can be achieved. Akathisia is less likely to respond to antiparkinsonian medication, however, although it may respond to benzodiazepines or beta-blockers (Fleischhaker et al. 1990).

Disappointment Reactions
People with schizophrenia may easily have as much, if not more, to be disappointed about in the way in which their lives are progressing as individuals who do not have schizophrenia, and their interpersonal or communication difficulties may make it more difficult than it otherwise would be to distinguish this situation from depression at any given point in time. Acute disappointment reactions can be distinguished by the parallel history of a suitable recent event (if that can be elicited) and a transient course (seldom more than a few days to a couple weeks).

Chronic disappointment reactions are known as demoralization (de Figueiredo 1993; Frank 1973; Klein 1974) and can be more difficult to distinguish from depression. A chronic history of disappointment or failure can lead a person with schizophrenia to the conviction that a useful or satisfying life is impossible. Indeed, it has been empirically validated that schizophrenia patients who feel less of a sense of control regarding their illness are more likely to experience depression (Birchwood et al. 1993). Of course, it is also reasonable to believe that the demoralization state is worthy of diagnosis and understanding because it is particularly likely to be amenable to appropriate psychosocial interventions.

Prodrome of Psychotic Relapse
Studies that have reviewed or examined the process of decompensation into psychotic episodes in schizophrenia often have noted symptoms common to depression to be manifest at these times (Docherty et al. 1978;

Green et al. 1990; Herz 1985; Herz and Melville 1980; Hirsch et al. 1989; Johnson 1988; Tollefson et al. 1999). Anxiety and withdrawal are frequent accompaniments of dysphoria in this situation, and signs or symptoms of early psychotic decompensation, such as hypervigilance or overinterpretation of events, may provide a valuable clue as to the true nature of the psychotic prodrome. Usually the depressed-appearing state is short-lived when it is a component of the psychotic prodrome, lasting for a couple days to a week, before more prominent and definitive symptoms of psychosis become manifest.