Lyme borreliosis and other tick-borne infections are clinical diagnoses. Although no test can rule out the possibility of infection,2,25,26 common laboratory testing may include Lyme IgGWestern blot from a reliable laboratory, brain SPECT, and cognitive testing. Other diagnostic assessment may include polymerase chain reaction, C-6 enzyme-linked immunosorbent assays in spinal fluid, flow cytometry, and testing for coinfections. CD57 natural killer cell panel testing is useful for tracking clinical progress.27

Caution should be taken because some patients may have an exacerbation of symptoms caused by a Jarisch-Herxheimer reaction (a short-term immunological reaction to antibiotic treatment that may include fevers, chills, head-aches, and myalgias) and may become acutely suicidal, violent, psychotic, and/or confused in response to antibiotic treatment.9 A trial course of antibiotics that causes a worsening of psychiatric symptoms followed by improvement suggests a Jarisch-Herxheimer reaction and can help support the impression that a chronic infectious process is contributing to psychiatric symptoms.

The differential diagnosis may include any medical or psychiatric condition, but particularly other conditions with complex presentations and fatigue, such as MS, lupus, and posttraumatic stress disorder.

Although co-occurring symptoms may be caused by multiple diseases, more commonly a single disease process can have multiple manifestations. The greater the comorbidity, the greater the likelihood that it is a systemic disease process with multiple manifestations. Multiple psychiatric syndromes, especially those with neurological and cognitive symptoms, suggest a CNS pathological process, while significant psychiatric and somatic comorbidity suggest systemic disease. Significant comorbidity increases the suspicion of Lyme borreliosis and other tick-borne infections.


Psychiatric and somatic comorbidity is the norm and Lyme borreliosis can often be associated with atypical presentations of psychiatric syndromes with relapsing and remitting progressive deterioration.12,13 For example, there may be an atypical presentation of attention-deficit/hyperactivity disorder (ADHD) with a predominance of executive dysfunction and sensory hyperacusis, panic disorder with attacks that last longer than 30 minutes, or presenile dementia.28 In addition, borreliosis can exacerbate preexisting psychiatric illness. It has been my clinical observation that this is particularly apparent with preexisting ADHD, depression, and psychotic disorders. Chronically mentally ill homeless persons frequently sleep in parks, increasing their risk for Lyme borreliosis and other tick-borne infections, which could exacerbate illness severity.


Although there is no FDA-approved treatment for the psychiatric symptoms associated with Lyme borreliosis, it has been my experience, as well as that of my colleagues, that many of the common psychopharmacological strategies for symptom reduction are beneficial. Patients with neuropsychiatric manifestations of Lyme borreliosis and other tick-borne infections often respond favorably to treatments that combine psychotropics and antimicrobials.2,29,30 Patients with inadequately treated late-stage infection may experience significant impairment and disability. Based on the collective experience of colleagues, the leading cause of death in borreliosis and tick-borne infections is believed to be suicide.31 Inadequately treated borreliosis and other tick-borne infections have been associated with autism spectrum disorder.11,32

A mild case may improve following treatment with either psychotropics or antibiotics. Patients who have mostly been treated with antibiotics often need psychotropics, while patients who have mostly been treated with psychotropics often need antibiotics. The physician should prioritize which symptoms are most severe and contribute most toward perpetuating chronic illness and treat those first. If psychotropics are needed, the choice of drug type depends on the presenting symptoms.

Commonly, the most disabling neuropsychiatric symptoms include sleep disorders, fatigue, cognitive impairments, depression, anxiety, pain, and headaches. Becauseimpaired sleep andchronic stress cause compromised immune functioning and contribute to fatigue and cognitive impairment, normalizing the circadian rhythm is often a treatment priority. Delta-sleep-promoting agents, such as pregabalin, trazodone, quetiapine, and tiagabine, are treatment options. Modafinil is often effective for excessive sleepiness, fatigue, cognitive impairment, and apathy.29,30,33

Memantine can improve white matter dysfunction and processing speed, reduce word inventions (neologisms), improve word retrieval, and reduce "static and crackle in the head." In addition, better verbal comprehension, and better focus have been reported.30 Atypicals can treat acute suicide risk. Mood stabilizers (anticonvulsants, atypicals, and lithium) can reduce aggression, migraines, and/or neuropathy and control seizures.29,30,34 Serotonin norepinephrine reuptake inhibitors can treat pain, anxiety, and depression. Doxepin in low doses is helpful for irritable gut. Acetylcholinesterase inhibitors are helpful for long-term memory impairments in late-stage disease. Although none of these are approved for treatment of neuropsychiatric symptoms associated with Lyme disease or other tick-borne infections, neither are they contraindicated, and there are no currently approved treatments. (We must treat with the best that we have, however flawed the evidence may be.) Prolonged antibiotic therapy may be useful and justifiable in patients with persistent symptoms of Lyme disease and coinfection with other tick-borne agents.2,10,35

The controversy

Controversial issues surrounding Lyme disease include the reliability of laboratory tests, persistence of infections, clinical manifestations, pathophysiology, and treatment strategies. In 1975, a rheumatologist undertook an investigation using an acute infectious disease model that focused primarily on the objective early, musculoskeletal (arthritis) symptoms and CNS symptoms; mental health capabilities were not considered. Some clinicians still believe that there is no later-stage encephalopathy and maintain the original, highly restrictive definition of Lyme disease from 1975. However, many reports have discussed the expanded complexity of the clinical presentations and pathophysiology, and the role of tick-borne and non-tick-borne interactive coinfections.35-38

Recognition of the mental impairments associated with these infections has been incorporated into a broader set of evidence-based guidelines from the National Guideline Clearinghouse for the treatment of Lyme disease.39 Other evidence-based guidelines, endorsed by the Infectious Diseases Society of America (IDSA) and the American Academy of Neurology, are more restrictive and do not incorporate psychiatric morbidity associated with Lyme borreliosis and other tick-borne infections.40,41 Insurance companies were quick to adopt the more restrictive guidelines and the legal system responded by investigating the IDSA guidelines.42

Since there are complex interactions between the brain, microbes, and the immune system, better communication is needed between psychiatrists, infectious disease specialists, and immunologists to reconcile the controversy.


Multisystemic diseases are often poorly managed because of the fragmentation in our health care system. In addition, patients with Lyme disease, similar to patients with psychiatric disorders, may have invisible disabilities and may have great difficulty with accessing adequate health care and disability coverage. Psychiatrists need to understand health care delivery issues and may be asked for opinions and assistance in these cases.

Additional information on neuro-psychiatric Lyme borreliosis is available from many online sources. Several of these are listed in Table 3.

Web sites with information on neuropsychiatric Lyme disease
• Lyme Info:
• Lyme Disease Research Studies:
• CDC Lyme Disease:
• Mental Health and Illness. Neuropsychiatric Assessment Database:
• National Guideline Clearinghouse:
• Lyme Disease Association, Inc:
• International Lyme and Associated Diseases Society (ILADS):
Accessed October 17, 2007.
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