Molecular Mechanism Behind Lithium’s Effectiveness Identified

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Scientists have identified the molecular mechanism behind lithium’s effectiveness in treating bipolar disorder in an international study published in Proceedings of the National Academy of Sciences (PNAS). Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP), Yokohama School of Medicine, Harvard Medical School, and UC San Diego collaborated on the study, which used human induced pluripotent stem cells (hiPS cells) to map lithium’s response pathway.

Lithium is a salt which has long been considered the gold-standard for bipolar treatment. The side effects–such as nausea, weight gain, and birth defects–are a trial for many people who take the drug. Only about one-third of people who suffer from bipolar disorder respond to lithium treatment. Before researchers at the Salk institute developed a test to predict who will respond to lithium with 92 percent accuracy, there was no test, and the drug’s effect was only found through a trial-and-error process which could take months or years.

In the study, scientists used hiPs cells created from lithium-responsive and non-responsive patience to observe a physiological difference in a protein called CRMP2: the protein was in a much more inactive state in responsive patients. However, when the researchers applied lithium, CRMP2 worked properly. So the study shows that bipolar disorder has a physiological–not necessarily genetic–cause.

This study is the first to explain the molecular basis of bipolar disorder. Scientists hope to use the results to develop a blood test for the disease, as well as further tests that can predict whether people who suffer from bipolar disorder will respond to lithium. Research leading from this study may also discover safer and more effective drugs to treat the disorder.

Edited to Add: Here is the link to the study, as requested.

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The History of the Treatment of Mental Illness

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Skull drills. Exorcisms. Isolation. Lobotomies. “Happy pills.” These are all treatments which have been applied–often forcibly–to people who suffer from mental illness.

 

The first apparent “cure” for mental illness was trephining (also referred to as trepanning). People in Neolithic times would chip holes–or trephines–in each others’ skulls with stone pieces, which was thought to release evil spirits from the head. This also happened to release pressure from brain inflammation. Some people actually survived this practice, as there have been skulls found with holes in them that showed signs of healing. This practice lasted for centuries, with more sophisticated equipment being invented, such as skull saws and drills.

To ancient peoples such as the Hebrews and the Persians, mental illnesses were attributed to supernatural forces, like demons and upset deities. Practices such as exorcisms and prayer were common in the ancient world. Egyptians appeared to be the most advanced civilization when it came to treatment of mental illnesses, recommending activities such as painting and attending concerts.

The Greek physician Hippocrates introduced the four humors–blood, bile, phlegm, and black bile–theory, which said that the combination of these fluids made up personalities. In the Middle Ages, mental illness was said to stem from an imbalance of the four humors. To bring the body back into balance, vomiting was induced, people were given laxatives, and leeches were applied. Sufferers of mental illness were also told to avoid red meat and wines. Beatings were also routinely applied to the mentally ill.

The first mental hospital was established in 792 AD, in Baghdad, followed by those in Aleppo and Damascus. However, at this time, the mentally ill were left to be cared by their families, and were often subject to abuse, concealment, or abandonment. Clergy-run facilities were soon established, which promised humane care. However, these could not handle the treatment of the entire population of the mentally ill.

Asylums were the next step, set up worldwide around the 1500s. The first in Europe is thought to be the Valencia mental hospital in Spain, 1406 AD, and though not much is known about this particular asylum, many treated their patients deplorably. Asylums, up until the mid-1800s, were places where the mentally ill slept shackled to the walls in their own waste. “Cures” ranged from bloodletting to dousing in hot and cold water to shock the system back to rationality. Physical restraints, threats, and straightjackets were common, implemented to get the sufferer to “choose” sanity. In Saint Mary of Bethlehem asylum in London, visitors could pay a penny to see violent patients in a freak show.

This all changed, starting in 1792 with a man named Philippe Pinel, in Paris. He took over La Bicentre asylum to test his hypothesis that compassion would cure the mentally ill. Patients were unchained and given clean, sunny rooms, and were no longer treated like animals. This humanitarian approach spread, kicking off a brief period of “moral management,” where patients were encouraged to perform manual labor and make moral choices.

Medical advances ended moral management. By 1939, Sigmund Freud had published twenty-four volumes of work in psychoanalysis, changing the world forever.  Freud tried hypnosis, free association, and dream interpretation. Although Freud’s work provoked criticism, psychoanalysis was popular until the mid-1900s.

During this time, psychopharmacology, surgeries, and electro-convulsive shock therapy (ECT) were common. The latter treatment was used to abuse patients in some mental hospitals, however. Because ECT is scary, patients were frequently intimidated and threatened with the practice. Some people were shocked over a hundred times. However, with reforms, this practice is still used today.

Egas Moniz performed the first lobotomy in 1935, first shocking the patient into a coma, and then hammering an instrument similar to an icepick through the top of each eye socket. This practice severs the emotional centers of the brain from the frontal lobes, producing a calm and immature patient that is unable to control their impulses or feel anything. Lobotomies were cheap, easy, and popular around the world for twenty years–until doctors started noticing the undesirable side effects.

With the introduction of the psychotropic drug Lithium in 1949, Australian psychiatrist J.F.J. Cade kicked off a wave of successful anti-psychotic medicines which effectively managed symptoms. Unfortunately, this also kicked off a wave of deinstitutionalization in the 1960s, as mental illnesses were thought to be managed entirely by medication. Thousands of the mentally ill discharged from mental wards ended up homeless. In the 1980s, over a third of all homeless individuals were severely mentally ill in America. Over 100,000 individuals who suffered from severe mental illness were imprisoned, and over a fourth of that population were held without charges as they waited for beds at one of the nation’s sole remaining mental hospitals.

Despite advancements made in therapies, many mentally ill people rely solely on psychotropic medications to avoid the shame of stigma. Mental health care is grossly underfunded in many countries around the world even today, and is widely stigmatized. The treatment of mental illness has come a long way, but we still have so much further to g

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Substance Abuse and Bipolar Disorder

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Sometimes, the symptoms of bipolar disorder–including periods of elevated mood, depression, and irritability–are too difficult to deal with. Often, people turn to drugs and alcohol to try to cope.

“Some people attempt to treat symptoms of their mental illness with substances, but substance abuse can activate or prolong symptoms,” Marissa Krick, a writer for DrugRehab.com, said in an email.

Krick cited studies saying that up to 60 percent of people who suffer from bipolar disorder confess that they’ve also abused drugs or alcohol. People who suffer symptoms of acute mania or bipolar II disorder are significantly more likely to abuse benzodiazepine and alcohol than people who suffer from depression, according to the Zurich Cohort Study. In addition, a history of substance abuse complicates recovery from acute manic states.

The writers at DrugRehab.com have penned an extensive report on substance abuse in conjunction with bipolar disorder. It’s worth a read. According to the report, “Substance abuse makes symptoms of bipolar disorder worse and decreases the benefits of standard treatment. People tend to take longer to recover, spend more time in health facilities and be more likely to contemplate suicide when they misuse substances during treatment.”

But there is hope. Rehabilitation facilities can treat both substance abuse and bipolar disorder concurrently. Treatment for substance abuse starts with a detoxification process, whereas treatment for bipolar disorder involves medication and behavioral therapy. Patients going through drug or alcohol withdrawal are kept as comfortable as possible.

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What to do if You Run Out of Medication

Medications. Like it or not, sufferers of mental health problems usually need to take them to manage their conditions. Being compliant with your prescribed pills is the best path to stable moods. But what happens when you run out?  Here are a few tips to deal with just that.

1. Don’t Panic

If you have a mental health issue that’s triggered by stress, panicking is the worst thing you can do for yourself. Withdrawal symptoms can be harsh, but not as bad as triggering your illness. Breathe. Remind yourself that this is a temporary problem, which can be fixed. Which brings us to our next point…

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2. Call Your Doctor

Call your doctor immediately, and keep them apprised of the situation. If you can’t meet with them, find out if they will call in a prescription for you to a pharmacy. Any doctor at your regular office should have access to your files, and should be able to fill a prescription.

3. Use a Regular Pharmacy

If you can, visit the same pharmacy and get to know your pharmacist. Bring your empty prescription bottles with you to talk to the technicians, and they might be able to give you an emergency five- or seven-day supply, or direct you to an emergency clinic that can. You are unlikely to get one if you are sixteen or younger, as pharmacists are reluctant to give out medication to minors. Take an adult that you trust with you to help smooth things over.

4. What if I Can’t Afford Them?

If you can’t afford your medications, ask your doctor. He or she may have access to free samples of the pills you need, or be able to prescribe you a cheaper generic drug. If you’re an American citizen and you’re uninsured, find out if the pharmaceutical company that manufactures your drug has a patient-assistance program. You may qualify for these programs if your income is 100% of the poverty line, but it’s unlikely that you will if you receive Medicaid benefits. Ask your pharmacy if they have a discount program if you pay in cash. If you’re over fifty and have a membership with the AARP, you can receive discounts on pills.

There is no reason for you to go into medication withdrawal. Ideally, you’d be able to have your doctor prescribe some drugs months in advance, but if that’s not the case, contact your doctors and pharmacy to find out what they can do for you. They want to work with you.

Have you ever run out of meds?

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