Underutilised augmentation strategies for mood disorders

To the Editor

Far more so than any other area of medicine, psychiatry requires the need for nuance in prescribing decisions and the ability to treat the patient as an individual rather than an ‘n’ in a randomised controlled trial (RCT). While mood disorders do share many similar features, no two patient experiences are identical, and thus no two treatment plans should be either. I believe that there are several augmentation strategies for both bipolar depression and treatment-resistant depression which are at present being significantly underutilised in Australia.

The first of these underutilised augmentation strategies is the addition of a psychostimulant. At present, the RANZCP Guidelines suggest that there is ‘insufficient evidence to recommend the routine use of psychostimulants as an augmentation strategy’ (Malhi et al., 2015: 1125). There are indeed good reasons to be cautious, but many of the theoretical arguments – such as switch into hypomania, abuse and so on – have seldom manifested into reality. While it is true that Shire was not able to get the desired endpoint of its study into lisdexamfetamine use in major depressive disorder, there are many individuals who would benefit from this drug (or methylphenidate), especially those with severe fatigue – an oft-forgotten but severely debilitating aspect of a depressive phase. Moreover, modafinil is also showing promising signs and should be taken much more seriously. Goss et al. (2013) considered six RCT studies (910 patients) of adjunct modafinil use in acute depression and bipolar depression, finding that it showed ‘significant positive effect on fatigue symptoms (95% CI, −0.42 to −0.05). The adverse events were no different to placebo’ (p. 1101). We must also strongly consider the role of psychostimulants being used on an ‘as needs’ rather than routine basis.

The norepinephrine-dopamine re-uptake inhibitor (NDRI) bupropion is also being underused in Australia. We know the role that norepinephrine and dopamine play in motivation, concentration and interest. In bipolar depression, it can be added to lamotrigine, while in treatment resistant depression (TRD) it can be added to an selective serotonin reuptake inhibitor (SSRI) (with the latter possibly creating positive synergistic effects).

Finally, agomelatine. While perhaps not efficacious enough on its own, it is nonetheless a very useful ‘helping hand’ augmentation strategy – especially in instances where depression is causing disturbances to sleep-wake patterns. We know that agomelatine can help greatly to resynchronise circadian rhythm. It also has a very minimal side effect profile (the low chance of hepatotoxicity can easily be managed with blood tests, and using 25 mg rather than 50). It may be a good option for patients who find that SSRIs cause an unacceptable level of emotional blunting (as was shown in Corruble et al., 2013) and has the added bonus of treating anxiolytic features.

We must always remember that no two experiences of a mood disorder are the same, and thus treatment guidelines (and Pharmaceutical Benefits Scheme (PBS) listing) must accommodate for this by allowing for more unorthodox augmentation options and usage patterns.