Lithium headaches

Divalproex sodium is comprised of sodium valproate and valproic acid. The delayed-release and extended-release formulations are converted in the small intestine into valproic add, which is the systemically absorbed form. It was developed as an antiepileptic drug, but also has efficacy for mood stabilization and migraine headaches. It is FDA-approved for the treatment of the manic phase of bipolar disorder. It is generally equal in efficacy to lithium and some other drugs for bipolar mania. It has particular utility in bipolar disorder patients with rapid cycling, mixed mood features, and substance abuse comorbidity. Although not FDA-approved for relapse prevention, studies support this use, and it is widely prescribed for maintenance therapy. Divalproex can be used as monotherapy or in combination with lithium or an antipsychotic drug.31... 

Lithium remains the treatment of choice for bipolar patients who experience classic euphoric episodes of mania. Current evidence suggests that those with mixed episodes or rapid cycling episodes respond preferably to anticonvulsants or atypical antipsychotic drugs. In addition to its use as a mood stabilizer, lithium is effective in converting unipolar antidepressant nonresponders to responders. Finally, lithium may also be an effective treatment for patients with clnster headaches. 

The authors commented that the manic symptoms had probably been caused by glucocorticoids or glucocorticoid withdrawal. They concluded that patients with cluster headache and a history of affective disorder should not be treated with glucocorticoids, but with valproate or lithium, which are effective in both conditions. Lamotrigine, an anticonvulsive drug with mood-stabilizing effects, may prevent glucocorticoid-induced mania in patients for whom valproate or lithium are not possible (101). 

A 64-year-old woman had a 2-week history of daily bilateral holocranial headache as the presenting complaint of lithium toxicity (serum concentration 2.5 mmol/1) dosage reduction resolved the headache and the extrapyramidal and cerebellar effects (199). 

Pseudotumor cerebri (benign intracranial hypertension) has been linked to lithium in over 30 cases, with headache, papilledema, increased intracranial pressure, reduced vision, and a risk of blindness (201). The condition tends to improve on withdrawal, but surgical intervention may sometimes be necessary. A review of pseudotumor cerebri devoted one paragraph to induction of this condition by lithium and provided six references but no new information (202). 

A 17-year-old woman developed pseudotumor cerebri with headache after she had taken lithium for 6.5 weeks (203). Papilledema and increased intracranial pressure resolved fully when lithium was withdrawn, and she was given acetazolamide. 

Bigal ME, Bordini CA, Speciali JG. Daily headache as a manifestation of lithium intoxication. Neurology 2001 57(9) 1733 1. 

Iyer V. Ketorolac (Toradol) induced lithium toxicity. Headache 1994 34(7) 442 1. 

Patients with bipolar disorders may benefit from risperidone. This has been observed in an open trial of ten patients with rapid cycling bipolar disorder who were refractory to lithium carbonate, carbamazepine, and valproate eight improved after 6 months of treatment. One patient dropped out through non-adherence to therapy and one because of adverse effects (agitation, anxiety, insomnia, and headache) (5). There was a similar beneficial effect in eight adults with moderate to profound mental retardation (6). Risperidone was associated with a significant reduction in aggression and self-injurious behavior, whereas adverse effects were primarily those of sedation and restlessness. 

Chronic cluster headache has responded to lithium (13). Sensory systems... 

Initial complaints, which usually diminish with time, include headache, lethargy, and muscle weakness. Nearly half of patients experience a fine hand tremor at some time during lithium treatment. For most people, this initial symptom remits however, for 10 percent of patients, it is a continuing side effect (American Society of Hospital Pharmacists 1993). Often the tremor becomes worse when the individual reaches for something. Sustained tremor, at therapeutic levels, can be managed with reassurance, and by limiting stimulants, such as caffeine, which may exacerbate the tremor. Sometimes this tremor is treated with beta blockers, usually propranolol (In-deral). 

Musculoskeletal Does the patient have muscular pain that could be caused by statins Does the patient have muscular spasms or central spasticity requiring an antispasmodic Does the patient complain of arthritic joint pain Are tension headaches a problem Does the patient have a tremor that could be attributed to medication use such as lithium, valproic acid, or beta agonists Does the patient have weakness that could be due to medication use, underuse, or overuse (e.g., pyridostigmine underuse, antispasmodic overuse) ... 

Lithium carbonate is effective against episodic and chronic cluster headache attacks, with beneficial effects often appearing during the first week of therapy. A positive response is seen in up to 78% of patients with chronic cluster headache and in up to 63% of patients with episodic cluster headache." The usual dose of lithium for cluster headache is 600 to 900 mg/day administered in divided doses. Tachyphylaxis to lithium has been reported occasionally during prolonged therapy." Optimal plasma lithium levels for the prevention of cluster headache have not been established, but efficacy has been reported at relatively low serum concentrations (0.3-0.8 mEq/L)." ... 

Initial side effects are mild and include tremor, lethargy, nausea, diarrhea, and abdominal discomfort. Lithium treatment has been associated with headache symptoms described as episodes of moderately severe, throbbing occipital pain lasting 6 to 12 hours, but these headaches are easily distinguishable from the cluster headache and disappear when lithium is withdrawn. Lithium should be administered with caution to patients with significant renal or cardiovascular disease, dehydration, pregnancy, or concomitant diuretic use. 

Ergotamine can be an efficacious agent for prophylactic as well as abortive therapy of cluster headaches." A 2-mg bedtime dose is often beneficial for the prevention of nocturnal headache attacks. Daily use of 1 to 2 mg ergotamine alone or in combination with verapamil or lithium may provide effective headache prophylaxis in patients refractory to other agents with little risk of ergotism or rebound headache." - ... 

Corticosteroids are useful for chronic cluster headaches refractory to verapamil, lithium, ergotamine, and methysergide or combinations of these agents." Therapy is initiated with 40 to 60 mg/day prednisone and tapered over approximately 3 weeks. Relief appears within 1 to 2 days of initiating therapy. To avoid steroid-induced complications, long-term use is not recommended. Headaches may recur when therapy is tapered or discontinued. 

During the past three decades, it has been possible to extend the classical antimanic, antidepressive and recurrent-prophylactic action profile of lithium by an antipsychotic (Alexander et al. 1979), antiaggressive (Nilsson 1994), antisuicidal (Mtiller-Oerlinghau-sen et al. 1992), antineurotic (PfafFenrath et al. 1982) and neuroprotective (Ermidou-Pollet and Pollet 2002) component. Though lithium is even the first-choice treatment in the prophylaxis of chronic and episodic courses of cluster headache in patients, who are aged over 45 years (Pfaf-fenrath et al. 1982), all the results with the antineurotic properties of lithium are based on open trials. Clear evidence of the antineurotic effect of lithium has not yet... 

In the mid-nineteenth century, the alkaline properties of lithium salts were widely used to treat various uric acid diatheses which included the many manifestation of brain gout including headache, epilepsy, mania and depression (Amdisen and Hildebrandt, 1988). During the 1950s, the... 

These adverse interaction reports are isolated and unexplained. Two reports make the point that these drugs are commonly used for aene eaused by lithium, so any common interaction resulting in raised lithium levels would be expected to have come to light by now. The case of pseudotumor cerebri also appears rare, but note that the female gender and obesity are risk factors for its development and so greater caution may be warranted in this type of patient. The authors advise frequent enquiry about headaches and visual changes. 

A study in lithium-treated manic-depressive patients foimd that the clearance of lithium was about 20% lower in 23 patients also taking propranolol than in 292 similar patients on lithium alone. However, the clinical effects of this difference were not evaluated, so the significance of this finding is imclear. A 70-year-old man who had been stable on lithium for 16 years was additionally started on propranolol 30 mg daily for lithium-induced tremor. Six weeks later he was hospitalised because of vomiting, dizziness, headache and a fainting episode. His pulse rate was 35 to 40 bpm and his serum-lithium level was 0.3 mmol/L. When later discharged on lithium without propranolol his pulse rate had risen to a range of 64 to 80 bpm. ... 

Toxicology ACGIH TLV/TWA 1000 ppm STEL 1250 ppm LD50 (oral, rat) 43 g/kg LCLo (inh., rat, 6 h) 87,000 ppm mildly toxic by ing. and inh. primary skin irritant may cause eye irritation, drying/cracking of skin high cones, may cause CNS symptoms, dizziness, headache TSCA listed Environmental ThOD 0.09 Precaution Combustible exposed to heat or flame incompat. with chemically active metals (calcium, powd. aluminum, zinc, magnesium, beryllium, titanium, samarium, lithium, barium) may react explosively... 

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