Anxiety and depression: individual entities or two sides of the same coin?

Several factors have led to suggestions that anxiety and depression are actually the same disease: very frequently, they co-exist; there is an overlap of symptoms between the two conditions; a number of similar agents can be used to treat both mental states; the same neurotransmitters are involved in both anxiety and depressive disorders; and stress can predispose both. Selective serotonin reuptake inhibitors (SSRIs) have shown efficacy in a number of neuroses: depression; obsessive-compulsive disorder (OCD) and anxiety disorders (panic disorder [PD], social anxiety disorder [SAD], generalised anxiety disorder and post-traumatic stress disorder). Furthermore, other drugs, for example, tricyclic antidepressants and monoamine oxidase inhibitors, are effective in treating both depression and some anxiety disorders. Yet some drugs are only effective in anxiety, for example, benzodiazepines, and this suggests that the two states are actually different. Despite the broad range of conditions that are treated by SSRIs, a number of differences are clear when SSRIs are used in depressive and anxious states. When used in PD and OCD, the effective dose of the SSRI is often higher than when used to treat depression. Furthermore, SSRIs often work more slowly in patients with anxiety compared with those with depression. In order to assess which serotonergic pathways and mechanisms are involved in these conditions, tryptophan depletion tests can be performed. Tryptophan is the precursor to serotonin (5-HT), so if the SSRI treatment effects are dependent on an increase in synaptic 5-HT levels, depletion will result in a relapse in symptoms. However, if the SSRI treatment works through post-receptor events, then tryptophan depletion will have little effect on the individual's symptoms. In depression, tryptophan depletion induced relapse in patients treated and controlled on SSRIs, but not in those recovered on noradrenergic agents such as desipramine. In some anxious states (PD and SAD), our work has shown that relapse was also experienced following tryptophan depletion, indicating that the SSRIs are acting via increasing 5-HT levels at the synapse in these conditions. However, other studies have found no effect of the tryptophan depletion test. This suggests that in OCD, SSRIs act post-synaptically and therefore have a different mechanism of action in OCD patients compared with depressed patients. In summary, although most SSRIs are effective in the treatment of both depression and anxiety, differences in dose, time to onset of action and, in some cases, mechanism of action are evident when treating the two conditions.