“Lithium Damaged My Spine” Might not be a Delusion After All
Muhammad Zaidi, M.D.;
INTRODUCTION
Lithium has been the drug of choice for treatment and
maintenance of Bipolar Affective Disorder (BPAD) for the
past few decades, with extensive literature showing its
effectiveness when used as a mood stabilizing agent.
However, significant research shows that up to a third of
patients on lithium not only have a negligible or absent
response, but may also show deterioration of their clinical
symptoms. It is suggested that this negative effect of lithium
depends on various factors.
About half of all individuals may stop lithium treatment at
some point despite its proven benefits in preventing severe
affective episodes and suicide. A study suggested that
patients with type 1 BPAD or Schizophrenia (SCZ) were
more likely to discontinue lithium as well as refuse
medications than patients with type 2 or unspecified BPAD.
Significantly, the side effect profile of lithium, especially its
neurotoxic effects, has been discussed in depth in literature
over the last decade.
CASE PRESENTATION
Our case focuses on a 59 y/o male with a history of
multiple admissions to a forensic hospital care setting. While
his initial diagnosis was Psychotic disorder NOS, it was later
revised to Schizoaffective disorder during subsequent
admissions. He presented with affective psychotic features,
with a labile mood shifting from melancholic to euphoric and
concurrent auditory verbal hallucinations. He displayed
paranoid non-bizarre persecutory delusions, and also
alleged that one of his physicians “hated (him) and had put
(him) on lithium as a form of punishment.”
The patient claimed that lithium, as a result, had
negatively affected him and damaged his nerves. This led
the authors to explore the significance and implications of
the use of lithium in patients with schizoaffective disorder
and bipolar disorder.
METHODS
The authors performed a systematic literature review of
the negative effects of lithium as well as factors influencing
patient adherence to lithium treatment. Studies that have
observed the side effects of lithium when used in
Schizophrenia and BPAD were included. Studies with other
concurrent diagnoses and other mood stabilizers were
excluded.
muhammad.zaidi@dc.gov
Anurag Prathipati, M.B.,B.S.; J.P. Martell, B.A.; Sakshi Dhir, M.D.
DISCUSSION
There is a reported genetic overlap
between BPAD and SCZ and these genetic factors are
thought to influence treatment response to lithium. A study
that assessed for long-term response to lithium treatment
over 5 years found that patients with BPAD who had a low
polygenic load for SCZ responded better to Lithium (Fig. 1).
Polygenic analysis quantifies the combined effects of
genetic polymorphisms across a genome on a given
outcome. Additional studies have shown that among
patients with BPAD, those with a family history of SCZ
show a poorer response to lithium. Furthermore, other
studies suggest that lithium may be detrimental to SCZ
patients because of greater liability of developing lithium-
induced neurotoxic effects even at modest doses.
Figure 1: At each threshold, a lower polygenic load for SCZ
was associated with a favorable treatment response to lithium
in patients with BPAD
Figure 2: 7Li b-SSFP MRI (in cyan) overlaid on Sagittal 1H-
MRI images.
Regarding the neurotoxic effects of lithium, acute lithium
toxicity initially affects fast-acting neurons controlling
coordination, resulting in tremor and extremity
discoordination. Increased toxicity may cause progressive
development of slurred speech, muscular fasciculation,
seizures, nystagmus and extrapyramidal features. A study
suggests that lithium has also been shown to accumulate in
different areas of the CNS (Fig. 2), with higher affinity for
white versus grey matter. Demyelination has been reported
in chronic users, especially in the Cerebellum, causing (...)
(...) ataxia, dysarthria, and potentially permanent
cerebellar and pyramidal cell dysfunction. Studies have
also found that sustained lithium usage could precipitate
hypernatremia as a complication of lithium-induced DI and
further exacerbate the neurotoxic effects.
Common side effects and other factors have been
identified as a frequent cause of lithium discontinuation,
with lithium non-adherence being one of the main
causes(Fig. 3). Additionally, demographics, degree of
illness, and treatment-related factors do not predict non-
adherence with certainty. Rather, recent studies suggest
that greater emphasis on factors like patient attitude and
insight towards illness and treatment, clinician-patient
relationship, and the impact of immediate environment
could help better explain non-adherence to lithium.
Figure 3:Top 10 reasons for Lithium discontinuation
CONCLUSION
Although first line in therapy for BPAD, lithium has
several neurotoxic and other negative side effects.
These are especially detrimental in susceptible
populations due to factors like genetic characterizations
and non-adherence. Shifting towards a patient-centered
approach can help tailor a personalized treatment plan
and promote proper treatment adherence to lithium.
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