Next: Harnessing Neuroplasticity, Medication AND Psychotherapy to treat mental health conditions

There is mount­ing recog­ni­tion in the sci­en­tif­ic com­mu­ni­ty that com­bin­ing dif­fer­ent treat­ment approach­es for men­tal health con­di­tions can cre­ate a ben­e­fit greater than the sum of its parts.

As a clin­i­cal psy­chol­o­gist and neu­ro­science researcher, I have been work­ing to inte­grate insights from both fields to expand treat­ment options for those suf­fer­ing from depres­sion, anx­i­ety and relat­ed con­di­tions. Design­ing a treat­ment plan that pays care­ful atten­tion to the sequence and dose of both bio­log­i­cal and behav­ioral ther­a­pies might ben­e­fit peo­ple in new ways that nei­ther approach can achieve on its own.

Anx­i­ety and depres­sion are the most preva­lent men­tal health con­di­tions around the world. Glob­al­ly, about 280 mil­lion peo­ple expe­ri­ence depres­sion, and as many as 1 in 3 will meet the diag­nos­tic cri­te­ria for an anx­i­ety dis­or­der at some point in their lives. There are numer­ous effec­tive treat­ment options for both con­di­tions, includ­ing med­ica­tions, psy­chother­a­py, lifestyle changes and neurostimulation.

Doc­tors and ther­a­pists rec­om­mend many patients seek­ing men­tal health care try more than one approach simul­ta­ne­ous­ly, such as med­ica­tion and ther­a­py. This is based on the idea that if they were to respond well to any of the pre­scribed treat­ments, they would expe­ri­ence a net ben­e­fit more quick­ly or more strong­ly than if they were to try each sequen­tial­ly. How­ev­er, researchers have his­tor­i­cal­ly stud­ied each approach in iso­la­tion. Most research has focused on com­par­ing indi­vid­ual treat­ments one at a time to a con­trol, such as a pill place­bo or a psy­chother­a­py waitlist.

Neuroplasticity and treatment

Recent advances in sci­en­tif­ic under­stand­ing of depres­sion, anx­i­ety and oth­er stress-relat­ed con­di­tions sug­gest that changes and impair­ments in neu­ro­plas­tic­i­ty are crit­i­cal contributors.

Neu­ro­plas­tic­i­ty refers to the brain’s capac­i­ty to flex­i­bly adjust in response to an ever-chang­ing envi­ron­ment – it’s a crit­i­cal com­po­nent of learn­ing. In ani­mal stud­ies, deficits in neu­ro­plas­tic­i­ty are seen as changes to mol­e­c­u­lar and neur­al path­ways, such as a decreased num­ber of synaps­es, or points of con­tact between neu­rons, fol­low­ing chron­ic stress. These changes might be relat­ed to men­tal pat­terns and symp­toms of depres­sion and anx­i­ety in peo­ple, such as when patients report a reduced capac­i­ty to think, feel and act flex­i­bly. They may also be linked to think­ing about, remem­ber­ing and inter­pret­ing infor­ma­tion in a way that tends to be biased toward the negative.

Research has shown that many effec­tive bio­log­i­cal treat­ments, includ­ing med­ica­tions and neu­rostim­u­la­tion, can enhance or alter neu­ro­plas­tic­i­ty. Cer­tain lifestyle changes such as reg­u­lar exer­cise can have sim­i­lar effects. Sci­en­tists con­sid­er this key to how they reduce symp­toms. Unfor­tu­nate­ly, symp­toms often return when these treat­ments are dis­con­tin­ued. Relapse is par­tic­u­lar­ly appar­ent for med­ica­tions. For both old­er and new­er anti­de­pres­sant and anti-anx­i­ety med­ica­tions, relapse rates begin climb­ing short­ly after patients stop treatment.

In con­trast, behav­ioral treat­ments such as psy­chother­a­py intro­duce new skills and and habits that may be more long-last­ing. Ben­e­fits con­tin­ue even after the most intense phase of treat­ment ends. Reg­u­lar meet­ings with a ther­a­pist over the course of sev­er­al months can help many patients learn to cope with neg­a­tive symp­toms and life cir­cum­stances in new ways. But such learn­ing depends on neu­ro­plas­tic­i­ty to forge and retain these new, help­ful path­ways in the brain.

Researchers hypoth­e­size that enhanc­ing or mod­u­lat­ing plas­tic­i­ty with a bio­log­i­cal inter­ven­tion like med­ica­tion may not only reduce symp­toms but may also pro­vide a win­dow of oppor­tu­ni­ty for behav­ioral inter­ven­tions like psy­chother­a­py to be more effec­tive. Learn­ing-based inter­ven­tions like cog­ni­tive-behav­ioral or expo­sure ther­a­py, if prop­er­ly timed, could har­ness the enhanced neu­ro­plas­tic­i­ty that bio­log­i­cal inter­ven­tions induce and improve long-term outcomes.

Think of path­ways in the brain as roads. Bio­log­i­cal treat­ments trans­form a sparse­ly con­nect­ed set of roads – con­sist­ing only of a few well-trod­den path­ways that rep­re­sent unhelp­ful thoughts, fears and habits – into a denser net­work of inter­con­nect­ed, fresh­ly paved road­ways. Behav­ioral treat­ments can be likened to repeat­ed­ly dri­ving over a spe­cif­ic sub­set of new roads that lead to more bal­anced per­spec­tives on your­self and the world around you, learn­ing them until you can dri­ve down them effort­less­ly, no GPS required. This ensures that those now famil­iar road­ways will be read­i­ly avail­able to you in the future and pro­tect you against the return of anx­i­ety and depression.

Synergies in combined treatment

Design­ing com­bined treat­ments to explic­it­ly pro­mote syn­er­gy is rel­a­tive­ly new, and there is increas­ing evi­dence sup­port­ing it. A few spe­cif­ic exam­ples are noteworthy.

First, some stud­ies have shown that D‑cycloserine, an antibi­ot­ic used to treat tuber­cu­lo­sis, may make expo­sure ther­a­py for anx­i­ety con­di­tions more effec­tive by help­ing patients learn to quell their fears. D‑cycloserine may also enhance the anti­de­pres­sant effects of a type of neu­rostim­u­la­tion called tran­scra­nial mag­net­ic stim­u­la­tion, which stim­u­lates nerve cells using mag­net­ic fields.

Sev­er­al stud­ies sug­gest that pair­ing neu­rostim­u­la­tion with cog­ni­tive-behav­ioral approach­es like cog­ni­tive-behav­ioral ther­a­py or cog­ni­tive con­trol train­ing may yield longer-term reduc­tions in depres­sion and anxiety.

Sim­i­lar­ly, low dos­es of ket­a­mine, a drug used in gen­er­al anes­the­sia, with rapid anti­de­pres­sant effects, can be used to “prime the pump” for new, help­ful learn­ing. A study my team and I con­duct­ed found that dai­ly com­put­er-based exer­cis­es of 30 to 40 min­utes over four days fol­low­ing a sin­gle ket­a­mine dose led to a nine­fold increase in the dura­tion of anti­de­pres­sant effects – 90 days of reduced symp­toms – com­pared with ket­a­mine alone, which led to 10 days of reduced symptoms.

Final­ly, there is increas­ing inter­est in using oth­er med­ica­tions with psy­che­del­ic prop­er­ties to assist in psy­chother­a­py. The ther­a­peu­tic ben­e­fits of tak­ing these psy­che­del­ic-assist­ed ther­a­pies under med­ical super­vi­sion are attrib­uted to the rapid neu­ro­plas­tic­i­ty-enhanc­ing and con­scious­ness-alter­ing effects of drugs like psilo­cy­bin and MDMA. Researchers think these short-term effects fos­ter new insights and per­spec­tives that psy­chother­a­pists can help patients inte­grate into their per­ma­nent worldview.

There is great poten­tial in neu­ro­science-guid­ed ways to com­bine treat­ments. How­ev­er, it’s impor­tant to note that dif­fer­ent treat­ment approach­es can occa­sion­al­ly work against each oth­er, less­en­ing the long-term ben­e­fits of psy­chother­a­py alone. For exam­ple, one study on pan­ic dis­or­der found that patients who learned psy­chother­a­py tech­niques while tak­ing anti-anx­i­ety med­ica­tion had a greater chance of relapse after dis­con­tin­u­ing their use com­pared with those giv­en psy­chother­a­py alone.

Care­ful­ly designed clin­i­cal tri­als and long-term fol­low-ups are need­ed to ful­ly under­stand how to com­bine the bio­log­i­cal and the behav­ioral to devel­op treat­ments that are effi­cient, acces­si­ble, safe and enduring.

– Rebec­ca B. Price, PhD is an Asso­ciate Pro­fes­sor in the Depart­ments of Psy­chi­a­try and Psy­chol­o­gy at the Uni­ver­si­ty of Pitts­burgh. Her research pro­gram is broad­ly ded­i­cat­ed to push­ing the field of cog­ni­tive neu­ro­science towards a more direct clin­i­cal impact. This arti­cle was orig­i­nal­ly pub­lished on The Con­ver­sa­tion.

To Learn More:

• Does ADHD treat­ment enable long-term aca­d­e­m­ic suc­cess? (Yes, espe­cial­ly when phar­ma­co­log­i­cal and non-phar­ma treat­ments are combined)
• Sur­vey of 2500 fam­i­lies finds what ADHD treat­ments seem to work/ not work as applied in the real world
• What are cog­ni­tive abil­i­ties and how to boost them?