Treating ‘depression’ in patients with schizophrenia

⁴ While the acute disappointment reaction is ongoing, the emotional burden may be substantial. With bereavement or grief reactions the loss is clear; however, be vigilant for situations where the patient’s loss may be idiosyncratic or symbolic.

Chronic disappointment reactions, also known as the demoralization syndrome, involve long-term convictions of defeat, despair, incompetence, and loss of control.¹⁰ These reactions can be devastating and prolonged. These reactions are important to identify because they may be ameliorated by rehabilitative interventions or other psychosocial supports.

Prodrome of psychotic relapse. Longitudinal observations of patients with schizophrenia have found depressive symptoms may occur during the early stages of psychotic decompensation.^4,11,12 These symptoms include dysphoria, anxiety, agitation, sleep and/or appetite disturbances, impaired concentration, hopelessness, helplessness, feelings of loss of control or alienation, and social withdrawal. These features usually last a few days to a couple of weeks before they are overtaken by psychotic phenomena.

Depression may occur with similar frequency among patients with schizophrenia as the general population—an estimated 17%.¹³ Once other possibilities for a depression-like syndrome have been considered, it is reasonable to speculate that a patient’s symptoms might be the product of a traditional depression diathesis, and might respond to usual treatments for depression.

Treatment: A suggested approach

Based on my clinical experience in managing newly emergent “depression” episodes in patients correctly diagnosed with schizophrenia, I suggest the following approach:

First, assess the patient for medical disorders that could present with depressive features. Collaborate with the patient’s primary care physician to determine which medications the patient is taking and whether there have been any recent changes in these agents or their doses, including adherence issues, potential substance use or abuse, and changes between brand name and generic agents. Thoroughly evaluate the patient’s psychiatric status, including symptoms, suicidal risk, and changes in life circumstances. A patient who is at high risk of suicide may require hospitalization. Also assess for the presence of extrapyramidal side effects.

Do not change your patient’s medication regimen at this early stage, but provide him or her structure and support, and schedule an early appointment for the next visit (eg, 1 week later). A planned telephone call before the appointment may be helpful as well. If the “depression” is an acute disappointment reaction, it may run its course and resolve. However, if your patient’s depressive symptoms are a prodrome of psychotic relapse, the quick follow-up contact will improve the chances of preventing a psychotic episode by increasing the antipsychotic dosage or making other reasonable changes in pharmacotherapy.

If at the follow-up visit the patient’s psychotic symptoms have not progressed but depressive symptoms persist, evaluate for the possibility of parkinsonian symptoms, which may be subtle and difficult to rule out. If your patient is restless or tends to be physically active, a trial of a benzodiazepine can be added to treat akathisia. If the patient is underactive, consider a trial of an anticholinergic antiparkinsonian agent, such as benztropine, for akinesia. Dosages of benztropine can be raised in a stepwise manner up to 6 mg/d if there are no side effects, such as constipation, dry mouth, blurry vision, or memory impairment. Advantages of treating extrapyramidal side effects first include:

• response to antiparkinsonian medications occurs rapidly—if your patient shows no response within a week, future response at this dose is unlikely
  
• the presence of anticholinergic side effects is a biologic marker indicating that the treatment dose is adequate
  
• the clinician has more time to get to know the patient and his or her condition before committing to lowering, raising, or changing the antipsychotic dosage.
  

Once extrapyramidal symptoms have been ruled out, consider the possibility of antipsychotic-induced dysphoria. If the patient does not have current psychotic symptoms, cautious lowering of the antipsychotic can be tried. Lower the dose gradually and closely monitor for emerging psychotic symptoms. If your patient has evidence of psychotic symptoms or if the antipsychotic can’t readily be lowered, switching antipsychotics is a reasonable approach. Several second-generation antipsychotics have been associated with reduced symptoms of “depression,” (Table 2)^14-17 although it is not entirely clear whether the real difference is in depression or in negative or extrapyramidal symptoms.^1,2,17,18

Table 2

Antidepressant effects of antipsychotics in schizophrenia patients

Study	Design	Results
Marder et al, 199714	In 2 double-blind trials, 513 patients with chronic schizophrenia received risperidone (2, 6, 10, or 16 mg/d), haloperidol (20 mg/d), or placebo for 8 weeks	Patients receiving risperidone showed greater reductions in anxiety and depression symptoms as measured by PANSS scores than patients receiving haloperidol or placebo
Tollefson et al, 199815	In a prospective, blinded trial, 1,996 patients with schizophrenia received olanzapine (5 to 20 mg/d) or haloperidol (5 to 20 mg/d)	Among patients with depressive signs and symptoms, those who received olanzapine showed better improvement in MADRS scores than patients receiving haloperidol
Emsley et al, 200316	Patients with schizophrenia (N = 269) who had not responded to 4 weeks of fluphenazine (20 mg/d) were randomized to receive quetiapine (600 mg/d) or haloperidol (20 mg/d) for 8 weeks	Quetiapine produced greater reduction on PANSS depression scores than haloperidol
Mauri et al, 200817	In a retrospective study, 222 patients in the reexacerbation phase of schizophrenia received fluphenazine, haloperidol decanoate, haloperidol, clozapine, olanzapine, quetiapine, risperidone, or L-sulpiride monotherapy	All antipsychotics led to improvements in depressive symptoms as measured by the BPRS scale, but improvements were statistically significant only with fluphenazine, haloperidol, olanzapine, risperidone, and L-sulpiride
BPRS: Brief Psychiatric Rating Scale; MADRS: Montgomery-Åsberg Depression Rating Scale; PANSS: Positive and Negative Syndrome Scale