Oral medications
First-line
When symptoms are sufficiently troublesome to warrant treatment, the first medication choices are beta blockers such as propranolol or alternately, nadolol and timolol. Atenolol and pindolol are not effective for tremor. The anticonvulsant primidone may also be effective. ET is generally responsive to alcohol, but the risks of regular drinking are greater than the potential benefit. Nonetheless, ET patients sometimes self-medicate with alcohol.Propranolol and primidone only have tremor-reducing effects on about half of ET patients, and the effects are moderate. Second-line
Second-line medications are the anticonvulsants topiramate, gabapentin (as monotherapy) or levetiracetam, or  benzodiazepines such as alprazolam. Third-line
Third-line medications are clonazepam and mirtazapine. Fourth-line
Theophylline has been used by some practitioners to treat ET, though it may also induce tremor. However, its use is debated due to conflicting data on its efficacy. Some evidence shows that low doses may lead to improvement.Ethanol has shown superior efficacy to those of benzodiazepines in small trials. It improves tremor in small doses and its effects are usually noticeable within 20 minutes for 3–5 hours, but occasionally appears in a rebound tremor augmentation later.Some systematic reviews of medications for the treatment of ET have been conducted. A 2017 review of topiramate found limited data and low quality evidence to support its efficacy and the occurrence of treatment-limiting adverse effects, a 2017 review of zonisamide found insufficient information to assess efficacy and safety, and a 2016 review of pregabalin determined the effects to be uncertain due to the low quality of evidence.
Cade was injecting rodents with urine extracts taken from manic patients in an attempt to isolate a metabolic compound which might be causing mental symptoms. Since uric acid in gout was known to be psychoactive, (adenosine receptors on neurons are stimulated by it; caffeine blocks them), Cade needed soluble urate for a control. He used lithium urate, already known to be the most soluble urate compound, and observed that it caused the rodents to become tranquil. Cade traced the effect to the lithium ion itself, and after ingesting lithium himself to ensure its safety in humans, he proposed lithium salts as tranquilizers. He soon succeeded in controlling mania in chronically hospitalized patients with them. This was one of the first successful applications of a drug to treat mental illness, and it opened the door for the development of medicines for other mental problems in the next decades.The rest of the world was slow to adopt this treatment, largely because of deaths which resulted from even relatively minor overdosing, including those reported from use of lithium chloride as a substitute for table salt. Largely through the research and other efforts of Denmarks Mogens Schou and Paul Baastrup in Europe, and Samuel Gershon and Baron Shopsin in the U.S., this resistance was slowly overcome.