Difficulties in diagnosis and treatment—consequences for palliative psychiatry

We read with great interest the case report Elgudin et al. in the journal Annals of Palliative Medicine, which presented the case of a 49-year-old man with schizophrenia and severe chronic agitated/malignant catatonia who was hospitalized for ten months (1). This case raises several considerations from a differential diagnostic standpoint.

The patient developed malignant neuroleptic syndrome (MNS)/catatonia following prolonged olanzapine treatment. Over time, the patient was prescribed five different antipsychotics (AP), which led to an increase in creatine kinase (CK) levels and fever. Electroconvulsive therapy (ECT) or lorazepam proved effective, but each reintroduction of AP reignited MNS after varying intervals.

From the presented history, we propose the question, was it truly schizophrenia?

In classical psychiatric frameworks, such as those proposed by Bleuler, Kraepelin, and Wernicke-Kleist-Leonhard, there was a conceptual gap between affective disorders (which typically resolve completely) and schizophrenia (which results in residual symptoms).

Cycloid psychoses were identified within this gap, exhibiting:

• A thematic resemblance to schizophrenia with bipolar characteristics, as discussed by the team at the case’s conclusion:
  • Paranoid schizophrenia aligns with anxiety-happiness psychosis.
  • Catatonia correlates with hyperkinetic-akinetic motility psychosis.
  • Hebephrenia is akin to agitated-inhibited confusion.
• Sudden polarity shifts, prompting Leonhard to classify cycloid psychoses as emotional psychoses, distinct from affective disorders like bipolar depression.
• A specific treatment approach, where AP—including atypical ones—should generally be avoided due to their potential to trigger MNS.

In the International Classification of Diseases (ICD)-10, cycloid psychosis is broadly categorized under F23.0, F23.1, and F28.

However, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) and ICD-11 do not formally recognize cycloid psychoses!

A comparative study by Jabs et al. (2) assessed the quality of life in patients with schizophrenia (n=47) versus cycloid psychoses (n=33) where:

• 17 patients exhibited anxiety-happiness psychosis;
• 4 had motility psychosis;
• 12 experienced confusion psychosis.

Symptoms & features

Perris and Eisemann (3) outlined key diagnostic criteria for cycloid psychoses:

• An acute psychotic state not induced by substances, medication, or brain injury.
• Sudden onset, with complete psychotic transformation occurring within hours to days.
• The presence of at least four of the following symptoms:

Perplexity; mood-incongruent delusions; hallucinations (often centred on death); intense, unprovoked fear; overwhelming bliss or religious euphoria; motility disturbances (akinetic or hyperkinetic); fascination with death; mood fluctuations insufficient to qualify as an affective disorder.

Bräunig (4) emphasized syndromic instability as a hallmark feature, characterized by:

• Low temporal consistency of dominant psychopathological syndromes.
• Unstable and fluctuating symptoms.
• Alternating clinical presentations.
• Lucid intervals.
• Significant influence of external/internal factors on symptomatology.

Leonhard (5) described anxiety psychosis with:

• Anxious thoughts, typically accompanied by paranoid symptoms.
• Uncertainty in symptoms, fluctuating between paranoid ideation and hallucination.
• Episodes of intense distress, including moaning, screaming, pleading, or resisting interaction.
• Periods of complete immobility followed by sudden agitation.

Treatment considerations

Franzek et al. (6) observed that MNS occurs predominantly in cycloid psychosis patients. Distinguishing MNS from catatonia remains clinically challenging.

Kuhlwilm et al. (7) recommended discontinuing neuroleptics in cases of MNS. While most MNS cases (96%) arise within the first four weeks of neuroleptic therapy, late-onset and recurrent MNS remain under-researched.

Stöber et al. (8) advocated for lithium or valproic acid over AP for phase prophylaxis in cycloid psychoses.

Kirov (9) advised against long-term neuroleptic maintenance for cycloid psychosis patients.

Case analysis

Given the above considerations, the case can be summarized as follows:

• Cycloid psychoses resolve without residual effects. If residual symptoms persist, schizophrenia is more likely. The extended use of AP before MNS onset may have been unnecessary. This aligns with Kirov’s warning against prophylactic antipsychotic use in cycloid psychoses.
• The patient was admitted in 2021 for wandering behaviour, disorganization, and paranoia—symptoms consistent with cycloid psychoses as per Perris and Eisemann.
• MNS developed, marked by fever and elevated CK. Lorazepam alleviated the catatonia/MNS.
• Symptoms recurred with low-dose olanzapine and lorazepam reduction, resembling Bräunig’s description of cycloid symptomatology.
• After an intensive care unit (ICU) stay and administration of an older antipsychotic, the patient initially showed a lucid interval with blissful experiences (see Bräunig). However, lucid intervals can mimic remission.
• The patient then exhibited severe paranoia (see Leonhard), possibly contributing to increased aggression.
• In his fear, the patient became resistant to interaction, as described by Leonhard.
• Physical health deteriorated, leading to ICU readmission, sedation, and intubation. Upon withdrawal of AP, catatonic symptoms ceased.
• Pimavanserin initially induced feelings of happiness but was followed by catatonia, necessitating another ICU admission.
• The treatment approach was ultimately abandoned, and the patient succumbed to pneumonia.
• Could an earlier diagnosis of cycloid psychosis have prevented this outcome?

Summary

In our post hoc opinion, the issue lies in the diagnostic frameworks. A condition unrecognized by the DSM-V cannot be formally diagnosed. However, retrospectively verifying the differential diagnosis remains challenging.

A takeaway from this case: if MNS or febrile catatonia occurs under antipsychotic treatment, an alternative approach—such as antidepressants—should be considered under the suspicion of cycloid psychosis.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apm.amegroups.com/article/view/10.21037/apm-25-36/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Elgudin J, Johnsen C, Westermair AL, et al. Palliative psychiatry for a patient with treatment-refractory schizophrenia and severe chronic malignant catatonia: case report. Ann Palliat Med 2024;13:433-9. [Crossref] [PubMed]
2. Jabs B, Krause U, Althaus G, et al. Comparative study of life quality in patients with cycloid and schizophrenic psychoses. Nervenarzt 2004;75:460-6. [Crossref] [PubMed]
3. Perris C, Eisemann M. Cycloid psychoses and their status within the scope of the classification of endogenous psychoses. Psychiatr Neurol Med Psychol Beih 1986;33:48-53.
4. Bräunig P. Emotional psychopathology and cycloid psychoses. In: Bräunig P, editor. Emotional psychopathology and cycloid psychoses. Stuttgart, New York: Schattauer; 1996. p. 87-107.
5. Leonhard K, Beckmann H, editors. Classification of Endogenous Psychoses and their Differentiated Etiology. New York: Thieme; 1995.
6. Franzek E, Stöber G, Beckmann H. Malignant neuroleptic and life-threatening catatonic syndrome: an identical complication in the course of functional psychoses. Neuropsychiatrie 1994;8:151-8.
7. Kuhlwilm L, Schönfeldt-Lecuona C, Gahr M, et al. The neuroleptic malignant syndrome-a systematic case series analysis focusing on therapy regimes and outcome. Acta Psychiatr Scand 2020;142:233-41. [Crossref] [PubMed]
8. Stöber G, Lauer M, Merschdorf U, et al. Manic-depressive illness and cycloid psychoses: psychopathology and differential diagnosis of bipolar phasic psychoses. Krankenhauspsychiatrie 2003;14:7-13.
9. Kirov K. Emotional psychopathology and cycloid psychoses. In: Bräunig P, editor. Emotional psychopathology and cycloid psychoses. Stuttgart, New York: Schattauer; 1996. p. 220.