The subjective feelings associated with antipsychotics are difficult to evaluate, and it is not unusual in clinical practice that complaints of this type are either believed to be exaggerated or delusional. However, complaints such as antipsychotic-induced dysphoria cannot be dismissed, as they often affect the patient’s compliance, social functioning and quality of life.

Neuroleptic-induced deficit syndrome (NIDS)
The concept of antipsychotic-induced deficit syndrome (NIDS) originated during an International Roundtable Meeting in October 1992, partly as a result of ‘awakenings’ reported with clozapine.  The term NIDS was coined to focus attention on the adverse effects of antipsychotics on affect, cognition, and social function.

There is no generally accepted definition of NIDS, which needs to be clearly differentiated from the deficit syndrome of schizophrenia, and from postpsychotic depression. NIDS comprises four areas⁵³:

• Dyscognitive syndrome
• Antipsychotic dysphoria
• Akinetic depression
• Subjective aspects of akathisia.

Antipsychotic-induced dysphoria
Antipsychotic-induced dysphoria is an unpleasant behavioral side-effect of antipsychotic drugs. It has been recognized ever since antipsychotics were first introduced into clinical practice.

Hollister⁵⁴ performed a naturalistic history study in 80 normal individuals who received a single 50mg dose of chlorpromazine. Twenty-five percent of the patients complained of fatigue, sleepiness and overall unpleasant feelings.

Manifestations of NIDS
When it comes to  the manifestations of NIDS, most clinicians are familiar with the following patient complaints:

“I feel unable to concentrate”
“I feel like a zombie”
“I feel emotionally unresponsive”
“I feel like I’m in a chemical straitjacket”

A dysphoric response is a significant predictor of antipsychotic non-compliance⁵⁵.  NIDS may also manifest as anxiety and derealization, school and work avoidance, or painful sensory symptoms⁵⁶. Whether antipsychotic-induced dysphoria can also manifest as a cause of, or contributor to, depression is a controversial issue that remains to be resolved.

Determinants of Antipsychotic-Induced Dysphoria
A number of determinants have been idenitified (Table 8)⁵⁶.
 

Determinant  Antipsychotic dosage and type          Time of onset  Relationship to antipsychotic plasma levels      Other (previous exposure, rate of dosage  increment, duration of antipsychotic  exposure)  EPS:    Akinesia, rigidity, and tremor   Akathisia  Placebo response or misattribution  Comment  Probably dose-related  More commonly reported with high-potency  antipsychotics, and in association with  akinesia or severe EPS  Generally acute  No unusual or elevated drug plasma levels  reported - no obvious pharmacokinetic  explanation55.  No definitive findings         No conclusive evidence  Stronger evidence reported57  No comment

Table 8. Possible determinants of NIDS⁵⁶.

Is antipsychotic dysphoria a healthy response ?
Dysphoria probably results in a poor outcome.  However, while many antipsychotic dysphoric patients become non-compliant, others benefit from dysphoria because it prompts clinicians to prescribe lower, yet still effective, doses of antipsychotics, resulting in less severe EPS⁵⁸.

EPS and medication compliance
Antipsychotic non-compliance in schizophrenia is a major public health problem.  Approximately 74% of antipsychotic-responsive schizophrenic outpatients become non-compliant with their antipsychotic regimen within two years of discharge⁵⁸. Yet the problem has attracted little good quality, systematic research. Only recently has the importance of this hitherto unrecognized mental health issue been acknowledged.

Akinesia and akathisia appear to be the most commonly reported side-effects related to non-compliance^58,59.  Akathisia has been associated with both non-compliance and antipsychotic non-response⁶⁰.  Antipsychotic non-compliance has also been associated with increased rates of completed suicide, assault and homicide.  For all of these reasons, EPS should be aggressively managed.

Conclusion
It is hoped that newer atypical antipsychotic agents with low EPS-inducing potential will obviate both the subjective and objective unwanted side-effects of the typical or standard antipsychotics⁶¹.  In doing so, new drugs will increase a patient’s ability and motivation to participate in treatment and rehabilitation, and thus improve his or her quality of life.

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