Psychopharmacology… Going Forward

future_of_medicineWhere Psychopharmacology heads in the future will be largely dependent upon how realistically it defines its goals. Given the multidimensional nature and complexity of what influences depression, is it at all reasonable to conclude that an antidepressant, or for that matter, any other medicinal substance will be able to arrest it, or at the least, manage it better than the agents available today? What about Bipolar disorder? What is it? For sure, not a single medication introduced to treat this disorder outperforms lithium day in and day out. And lithium made its debut in the late 1940s. Then there’s anxiety and insomnia. It’s quite evident that benzodiazepines are more than capable of reducing the excitability driven by fight-or-flight exacerbation and that there is a veritable host of sedating psychotropics capable of sledgehammering people to sleep. So people are pharmacologically calmed, is that all? As for schizophrenia and its multiple effects on different regions of the brain, can medication possibly ever effectively manage positive, negative and cognitive symptoms?

What needs to happen going forward? Here’s my assessment of where Psychopharmacology is now and where this discipline needs to go.

Depression and Antidepressants

The chemical imbalance theory is on its last legs. There are entirely too many people deemed clinically depressed who don’t have measurably low serotonin levels; and the plausibility of this theory is also challenged by low overall remission rates among antidepressant users. A shift to an expanded understanding of depression needs to move increasingly toward viewing it as a physical disorder. Further exploration of the depression-inflammation connection is currently the most reasonable direction to pursue. And while genotyping and phenotyping are worthy ventures in the search for reliable biomarkers in depression, such work will continue to be held hostage to the vagaries of funding. Also, the complexity of the brain often has scientists changing their minds.

As for antidepressants, research and development has certainly delivered on getting agents to the marketplace that are more tolerable – the major gain in this industry space. The SSRIs, SNRIs and other contemporary antidepressants are no more therapeutically effective than the pioneer Cyclic and MAOI classes, but unlike these older generation agents, there are fewer debilitating and annoying side effects.

Current antidepressants are more similar than different and truly novel, new drug chemistry has not been forthcoming, so the current group suffers from sameness. They’re all slow to work, testing the patience of the already vulnerable user. And lured by hope, many folks simply take then too long, develop tolerance, underestimate the difficulties associated with withdrawal and find they’re unable to get off the merry-go-round of going from one drug to another to another.

Antidepressants have alleviated misery for millions of users for over 60 years, but depression is likely far too complex for a pill to solve – regardless of how novel future agents may be.

Bipolar Disorder and Mood Stabilizers

puzzle_brainThis particular area of psychiatric diagnosis and treatment has been stuck in neutral for some time now. The etiology of the disorder remains quite the conundrum and neuroscience has not been able to adequately address this so as to have a positive impact on future direction. There are no animal models with validity so diagnosis is all over the place, and there is no consensus on neuropathology, thus pharmacology is all over the place.

Lithium and the anticonvulsant Depakote (divalproex) work reasonably well for mania under competent care. Second-generation antipsychotics have merely been repurposed and are not considered first-line agents for mania. The real stickler when it comes to treating this disorder is its depressive phase, as traditional, contemporary antidepressants are all but failures for managing bipolar depression, so this is likely the role that antipsychotics will fill.

Pharmacological treatment creativity seems to be a must with bipolar disorder and polypharmacy is not only necessary but warranted. Bipolar disorder is not nearly as well understood as unipolar depression, so the more light that advances in neurobiological discovery can shed into this dark space, the easier it will be for novel drug deliveries to emerge.

Anxiety and Anxiolytics

A certain amount of anxiety is simply a part of the human condition. We all have it from time-to-time – albeit brief and merely circumstantial for some, yet chronic for others. Anxiety is hitting on all cylinders when someone hands over control to it and increasingly avoids people, places and situations that stoke it and provoke it. Outside of moments or periods of startling, imminent danger or threat, most anxiety is happening between the ears; so it is best treated by challenging the self-limiting beliefs that give birth to it.

Anxiolytics such as the benzodiazepines work for most, but at what cost? The absence of anxiety, which can manifest as euphoria with increasing doses of these medications, paves the way for misuse, abuse, tolerance, dependence and drug-seeking as a primary goal. Withdrawal can be hell. Sleep agents deliver on getting people to sleep but falter on keeping them asleep. And they’re plagued by the potentially dangerous ramifications of sleepwalking as well as eating and driving without full, conscious awareness.

This space doesn’t need any more players. Anxiety and insomnia have to be faced, not numbed. There will be new contenders for sure though in this lucrative “discomfort” market.

Psychosis and Antipsychotics

We’re many orders of magnitude away from sufficiently understanding schizophrenia and its cousins. The psychotic spectrum remains highly stigmatized, sufferers are often feared and society struggles with making sense of its attendant array of aberrant behaviors.

Medication is effective for managing positive symptoms, but less so for negative and cognitive spectrum symptoms. And antipsychotics do virtually nothing for schizophrenia characteristics such as feelings of alienation, inadequacy and isolation. Future medication entries into this arena will have to spread their wings to provide more encompassing symptom coverage. The newer, second-generation antipsychotics, like their first-generation predecessors, can be horrible to take. Side effects are as long as an adult arm and are highlighted by medical issues such as an increased risk of type 2 diabetes, elevated cholesterol and lipids and significant weight gain, thereby bringing physical complications into play. New medications just cannot carry this kind of baggage.

ADHD and Psychostimulants

Every psychiatric syndrome on the planet adversely affects attention in some way, making it just way too easy to go to ADHD without discriminating assessment. And diagnosticians are taking advantage of this in droves. Stimulants are prime candidates for diversion and find their way into the hands of people intent on abusing them for their euphoric benefits or using them as brain boosters.

Clearly and definitively, psychostimulants work and make life less hard for the accurately diagnosed. The medication field in this domain is saturated; the success of new developments would best hinge upon ease of administration – delivery systems that include more extended-release liquids for those in need of dosage fine tuning and other patch formulations.

Regardless of future direction, psychopharmacology serves us best when it recognizes the importance of the human element in psychiatric treatment and acknowledges that many aspects of caring for those with mental illness doesn’t necessarily have to include chemicals.

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Attribution Statement:
Joe Wegmann is a licensed pharmacist & clinical social worker has presented psychopharmacology seminars to over 10,000 healthcare professionals in 46 states, and maintains an active psychotherapy practice specializing in the treatment of depression and anxiety. He is the author of Psychopharmacology: Straight Talk on Mental Health Medications, published by PESI, Inc.

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